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<title>γ-Secretase activity, clinical features, and biomarkers of autosomal dominant Alzheimer's disease: cross-sectional and longitudinal analysis of the Dominantly Inherited Alzheimer Network observational study (DIAN-OBS) - PubMed</title>
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||
|
||
<!-- ========== BEGIN HEADER ========== -->
|
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<section class="usa-banner">
|
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<div class="usa-accordion">
|
||
<header class="usa-banner-header">
|
||
<div class="usa-grid usa-banner-inner">
|
||
<img src="https://www.ncbi.nlm.nih.gov/coreutils/uswds/img/favicons/favicon-57.png" alt="U.S. flag" />
|
||
<p>An official website of the United States government</p>
|
||
<button
|
||
class="usa-accordion-button usa-banner-button"
|
||
aria-expanded="false"
|
||
aria-controls="gov-banner-top"
|
||
>
|
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<span class="usa-banner-button-text">Here's how you know</span>
|
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</button>
|
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</div>
|
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</header>
|
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<div
|
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class="usa-banner-content usa-grid usa-accordion-content"
|
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id="gov-banner-top"
|
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>
|
||
<div class="usa-banner-guidance-gov usa-width-one-half">
|
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<img
|
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class="usa-banner-icon usa-media_block-img"
|
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src="https://www.ncbi.nlm.nih.gov/coreutils/uswds/img/icon-dot-gov.svg"
|
||
alt="Dot gov"
|
||
/>
|
||
<div class="usa-media_block-body">
|
||
<p>
|
||
<strong>The .gov means it’s official.</strong>
|
||
<br />
|
||
Federal government websites often end in .gov or .mil. Before
|
||
sharing sensitive information, make sure you’re on a federal
|
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government site.
|
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</p>
|
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</div>
|
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</div>
|
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<div class="usa-banner-guidance-ssl usa-width-one-half">
|
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<img
|
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class="usa-banner-icon usa-media_block-img"
|
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src="https://www.ncbi.nlm.nih.gov/coreutils/uswds/img/icon-https.svg"
|
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alt="Https"
|
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/>
|
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<div class="usa-media_block-body">
|
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<p>
|
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<strong>The site is secure.</strong>
|
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<br />
|
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The <strong>https://</strong> ensures that you are connecting to the
|
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official website and that any information you provide is encrypted
|
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and transmitted securely.
|
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</p>
|
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</div>
|
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</div>
|
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</div>
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</div>
|
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</section>
|
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<div class="usa-overlay"></div>
|
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<header class="ncbi-header" role="banner" data-section="Header">
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<div class="usa-grid">
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<div class="usa-width-one-whole">
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<div class="ncbi-header__logo">
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<a href="https://www.ncbi.nlm.nih.gov/" class="logo" aria-label="NCBI Logo" data-ga-action="click_image" data-ga-label="NIH NLM Logo">
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<img src="https://www.ncbi.nlm.nih.gov/coreutils/nwds/img/logos/AgencyLogo.svg" alt="NIH NLM Logo" />
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</a>
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</div>
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<div class="ncbi-header__account">
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<a id="account_login" href="https://account.ncbi.nlm.nih.gov" class="usa-button header-button" style="display:none" data-ga-action="open_menu" data-ga-label="account_menu">Log in</a>
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<button id="account_info" class="header-button" style="display:none"
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aria-controls="account_popup">
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<span class="fa fa-user" aria-hidden="true"></span>
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<span class="username desktop-only" aria-hidden="true" id="uname_short"></span>
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<span class="sr-only">Show account info</span>
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</button>
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</div>
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<div class="ncbi-popup-anchor">
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<div class="ncbi-popup account-popup" id="account_popup" aria-hidden="true">
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<div class="ncbi-popup-head">
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<button class="ncbi-close-button" data-ga-action="close_menu" data-ga-label="account_menu"><span class="fa fa-times"></span><span class="usa-sr-only">Close</span></button>
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<h4>Account</h4>
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</div>
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<div class="account-user-info">
|
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Logged in as:<br/>
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<b><span class="username" id="uname_long">username</span></b>
|
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</div>
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<div class="account-links">
|
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<ul class="usa-unstyled-list">
|
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<li><a id="account_myncbi" href="/myncbi/" class="set-base-url" data-ga-action="click_menu_item" data-ga-label="account_myncbi">Dashboard</a></li>
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<li><a id="account_pubs" href="/myncbi/collections/bibliography/" class="set-base-url" data-ga-action="click_menu_item" data-ga-label="account_pubs">Publications</a></li>
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<li><a id="account_settings" href="/account/settings/" class="set-base-url" data-ga-action="click_menu_item" data-ga-label="account_settings">Account settings</a></li>
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<li><a id="account_logout" href="/account/signout/" class="set-base-url" data-ga-action="click_menu_item" data-ga-label="account_logout">Log out</a></li>
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</ul>
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</div>
|
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</div>
|
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</header>
|
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<div role="navigation" aria-label="access keys">
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<a id="nws_header_accesskey_0" href="https://www.ncbi.nlm.nih.gov/guide/browsers/#ncbi_accesskeys" class="usa-sr-only" accesskey="0" tabindex="-1">Access keys</a>
|
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<a id="nws_header_accesskey_1" href="https://www.ncbi.nlm.nih.gov" class="usa-sr-only" accesskey="1" tabindex="-1">NCBI Homepage</a>
|
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<a id="nws_header_accesskey_2" href="/myncbi/" class="set-base-url usa-sr-only" accesskey="2" tabindex="-1">MyNCBI Homepage</a>
|
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<a id="nws_header_accesskey_3" href="#maincontent" class="usa-sr-only" accesskey="3" tabindex="-1">Main Content</a>
|
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<a id="nws_header_accesskey_4" href="#" class="usa-sr-only" accesskey="4" tabindex="-1">Main Navigation</a>
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|
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<section data-section="Alerts">
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<div class="ncbi-alerts-placeholder"></div>
|
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</section>
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<!-- ========== END HEADER ========== -->
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|
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<a id="maincontent" aria-label="Main page content below" role="navigation"></a>
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|
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<input type="hidden" name="csrfmiddlewaretoken" value="sr59QRamzDy1XqCXGhVRUiVkDuRmLGScJePetHDI9elvRRINjAyToqrYbyzyEhqw">
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<form action="/" method="get" autocomplete="off" class="usa-search usa-search-big search-form content-page-layout" id="search-form" role="search">
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<div class="inner-wrap">
|
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<a class="pubmed-logo"
|
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aria-label="Pubmed Logo"
|
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href="/"
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data-ga-category="featured_link"
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data-ga-action="pubmed_logo">
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<img src="https://cdn.ncbi.nlm.nih.gov/pubmed/277eb475-38df-4990-a0ee-0080b04e86fc/core/images/pubmed-logo-blue.svg" alt="pubmed logo" />
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</a>
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<a href="#" class="search-input-trigger" data-alt-title="Hide search bar" title="Show search bar" aria-label="Show search bar">
|
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</a>
|
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<div role="search" class="search-input">
|
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|
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|
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<div class="form-field ">
|
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<label class="usa-sr-only" for="id_term">
|
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Search:
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</label>
|
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|
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|
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|
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<input
|
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type="search"
|
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name="term"
|
||
|
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data-skip-ie-scroll-to-top=""
|
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data-replace-term-with-exact=""
|
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data-exact-query=""
|
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placeholder=""
|
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class="term-input"
|
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required="required"
|
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id="id_term"/><a href="#" class="clear-btn" aria-label="Clear search input" title="Clear search input" role="button" data-pinger-ignore></a><button type="submit" class="search-btn" aria-label="Search" disabled data-pinger-ignore><span class="usa-search-submit-text">Search</span></button>
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|
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|
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|
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</div>
|
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|
||
</div>
|
||
|
||
<!-- Create alert and Create RSS are buttons that look like links -->
|
||
<!-- Better for them to look like buttons but no space -->
|
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<div class="search-links-wrapper content-page-layout">
|
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<div class="search-links">
|
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<a href="/advanced/"
|
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class="search-input-link adv-search-link"
|
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data-ga-category="featured_link"
|
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data-ga-action="adv_search">Advanced</a>
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<a href="/clipboard/"
|
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class="search-input-link clipboard-link hidden"
|
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data-ga-category="featured_link"
|
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data-ga-action="clipboard">
|
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Clipboard <span class="amount-in-clipboard"></span>
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</a>
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</div>
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|
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<span class="search-input-link user-guide-link" role="navigation" aria-label="User guide">
|
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<a href="/help/"
|
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data-ga-category="featured_link"
|
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data-ga-action="user_guide">
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User Guide
|
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</a>
|
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</span>
|
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|
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</div>
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</div>
|
||
|
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|
||
</form>
|
||
|
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|
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<div id="article-page-header">
|
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<div id="article-top-actions-bar" class="article-top-actions-bar">
|
||
<div class="inner-wrap">
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<div class="actions-container">
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<div class="return-to-search">
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|
||
</div>
|
||
|
||
<div class="multiple-results-actions " role="region" aria-label="save, email, send to">
|
||
<button id="save-results-panel-trigger"
|
||
type="button"
|
||
class="save-results save-results-panel-trigger"
|
||
aria-expanded="false"
|
||
aria-controls="save-action-panel"
|
||
data-ga-category="save_share"
|
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data-ga-action="save"
|
||
data-ga-label="open">
|
||
Save
|
||
</button><button id="email-results-panel-trigger"
|
||
type="button"
|
||
class="email-results email-results-panel-trigger"
|
||
aria-expanded="false"
|
||
aria-controls="email-action-panel"
|
||
data-ga-category="save_share"
|
||
data-ga-action="email"
|
||
data-ga-label="open">
|
||
Email
|
||
</button><div class="more-actions dropdown-block"><button id="more-actions-trigger"
|
||
type="button"
|
||
class="trigger more-actions-trigger"
|
||
ref="linksrc=show_moreactions_btn"
|
||
aria-label="Send to"
|
||
aria-controls="more-actions-dropdown">Send to</button><div id="more-actions-dropdown" class="dropdown dropdown-container" hidden><div class="content"><ul class="more-actions-links"><li><a class="clipboard-panel-trigger dropdown-block-link "
|
||
href="#"
|
||
role="button"
|
||
data-ga-category="save_share"
|
||
data-ga-action="clipboard"
|
||
data-ga-label="send">
|
||
Clipboard
|
||
</a></li><li><a role="button" class="dropdown-block-link bibliography-trigger-target" href="https://account.ncbi.nlm.nih.gov/?back_url=https%3A%2F%2Fpubmed.ncbi.nlm.nih.gov%2F39074479%2F%23open-bibliography-panel">My Bibliography</a></li><li><a role="button" class="dropdown-block-link collections-trigger-target" href="https://account.ncbi.nlm.nih.gov/?back_url=https%3A%2F%2Fpubmed.ncbi.nlm.nih.gov%2F39074479%2F%23open-collections-panel">Collections</a></li><li><a role="button" class="citation-manager-panel-trigger dropdown-block-link citation-manager-trigger-target" href="#">Citation manager</a></li></ul></div></div></div>
|
||
</div>
|
||
|
||
|
||
|
||
<div class="display-options" data-format-key="format"
|
||
data-default-format-value="abstract"
|
||
data-current-format-value="abstract" role="region">
|
||
<button
|
||
class="trigger usa-button"
|
||
title="Change format"
|
||
data-ga-category="display_options"
|
||
data-ga-action="display_options_dialog">
|
||
<span class="button-label">Display options</span>
|
||
</button>
|
||
|
||
<div class="dropdown" hidden>
|
||
<div class="title">
|
||
Display options
|
||
</div>
|
||
|
||
<div class="content">
|
||
|
||
<div class="format-container">
|
||
<span class="option-label">
|
||
Format
|
||
</span>
|
||
<select name="format" data-initial-value="abstract" aria-label="Display format" id="article-display-format">
|
||
<option value="abstract">Abstract</option>
|
||
|
||
<option value="pubmed">PubMed</option>
|
||
|
||
<option value="pmid">PMID</option>
|
||
|
||
</select>
|
||
</div>
|
||
|
||
</div>
|
||
</div>
|
||
</div>
|
||
<input type="hidden" name="csrfmiddlewaretoken" value="sr59QRamzDy1XqCXGhVRUiVkDuRmLGScJePetHDI9elvRRINjAyToqrYbyzyEhqw">
|
||
</div>
|
||
</div>
|
||
</div>
|
||
|
||
<div id="article-panels-container" class="article-panels-container">
|
||
<div id="save-action-panel" class="save-action-panel action-panel" aria-hidden="true">
|
||
<div class="inner-wrap">
|
||
<h2 class="action-panel-heading">
|
||
Save citation to file
|
||
</h2>
|
||
<form id="save-action-panel-form"
|
||
class="action-panel-content action-form"
|
||
action="/results-export-ids/"
|
||
data-by-search-action="/results-export-search-data/"
|
||
data-by-ids-action="/results-export-ids/"
|
||
method="post"
|
||
data-by-search-method="post"
|
||
data-by-ids-method="post">
|
||
|
||
<input type="hidden" name="csrfmiddlewaretoken" value="sr59QRamzDy1XqCXGhVRUiVkDuRmLGScJePetHDI9elvRRINjAyToqrYbyzyEhqw">
|
||
|
||
|
||
|
||
<div class="action-panel-control-wrap">
|
||
<label for="save-action-format" class="action-panel-label">
|
||
Format:
|
||
</label>
|
||
<select id="save-action-format" name="results-format" class="action-panel-selector">
|
||
<option value="summary-text">Summary (text)</option>
|
||
<option value="pubmed-text">PubMed</option>
|
||
<option value="pmid">PMID</option>
|
||
<option value="abstract">Abstract (text)</option>
|
||
<option value="csv">CSV</option>
|
||
</select>
|
||
</div>
|
||
|
||
<div class="action-panel-actions">
|
||
<button class="action-panel-submit"
|
||
type="submit"
|
||
data-loading-label="Saving..."
|
||
data-ga-category="save_share"
|
||
data-ga-action="save"
|
||
data-ga-label="save">
|
||
Create file
|
||
</button>
|
||
<button class="action-panel-cancel"
|
||
aria-label="Close 'Save citations to file' panel"
|
||
ref="linksrc=close_save_panel"
|
||
aria-controls="save-action-panel"
|
||
aria-expanded="false"
|
||
data-ga-category="save_share"
|
||
data-ga-action="save"
|
||
data-ga-label="cancel">
|
||
Cancel
|
||
</button>
|
||
</div>
|
||
</form>
|
||
</div>
|
||
</div>
|
||
|
||
|
||
|
||
|
||
<div id="email-action-panel"
|
||
class="email-action-panel action-panel"
|
||
aria-hidden="true"
|
||
data-recaptcha-script-url="https://www.recaptcha.net/recaptcha/enterprise.js?render=explicit&onload=onloadCaptchaCallback"
|
||
data-recaptcha-enabled="true">
|
||
<div class="inner-wrap">
|
||
<h2 class="action-panel-heading">
|
||
Email citation
|
||
</h2>
|
||
<form id="email-action-panel-form"
|
||
class="action-panel-content action-form"
|
||
action="/send-email/"
|
||
data-by-search-action="/results-export-email-by-search-data/"
|
||
data-by-ids-action="/send-email/"
|
||
data-by-search-method="post"
|
||
data-by-ids-method="post"
|
||
method="post"
|
||
>
|
||
<input type="hidden" name="csrfmiddlewaretoken" value="sr59QRamzDy1XqCXGhVRUiVkDuRmLGScJePetHDI9elvRRINjAyToqrYbyzyEhqw">
|
||
|
||
<div class="action-panel-control-wrap">
|
||
<span class="action-panel-label">
|
||
Subject:
|
||
</span>
|
||
<span class="email-subject" id="email-subject" aria-label="Email subject">1 selected item: 39074479 - PubMed</span>
|
||
<input type="hidden" name="email-subject" value="1 selected item: 39074479"/>
|
||
<input type="hidden" name="email-subject-hash" value="d1377f1c270e0dde2b486e9a1fdbd5860bd638bfdab9b6159c93d6f8d15e24c2"/>
|
||
</div>
|
||
|
||
<div class="action-panel-control-wrap">
|
||
<label for="email-to" class="action-panel-label required-field-asterisk">
|
||
To:
|
||
</label>
|
||
<input type="email" aria-label="Recipient Email Address" placeholder="email@example.com" id="email-to" class="email-to" pattern="^[a-zA-Z0-9_.+-]+@[a-zA-Z0-9-]+\.[a-zA-Z0-9-.]+$" maxlength="100" required>
|
||
</div>
|
||
|
||
<div class="action-panel-control-wrap">
|
||
<label for="email-from" class="action-panel-label">
|
||
From:
|
||
</label>
|
||
<input type="email" aria-label="Sender Email Address" placeholder="email@example.com" id="email-from" class="email-from" pattern="^[a-zA-Z0-9_.+-]+@[a-zA-Z0-9-]+\.[a-zA-Z0-9-.]+$" maxlength="256">
|
||
</div>
|
||
|
||
|
||
|
||
<div class="action-panel-control-wrap">
|
||
<label for="email-citation-format" class="action-panel-label">
|
||
Format:
|
||
</label>
|
||
<select id="email-citation-format" name="citation-format" class="action-panel-selector email-citation-format">
|
||
<option selected="selected" value="summary">Summary</option>
|
||
<option value="summary-text">Summary (text)</option>
|
||
<option value="abstract">Abstract</option>
|
||
<option value="abstract-text">Abstract (text)</option>
|
||
|
||
</select>
|
||
</div>
|
||
<div class="include-supplemental-container">
|
||
<input type="checkbox" aria-label="Include MeSH and other data" name="include-supplemental" id="email-include-supplemental" class="email-include-supplemental">
|
||
<label for="email-include-supplemental" class="email-include-supplemental-label">MeSH and other data</label>
|
||
</div>
|
||
|
||
|
||
|
||
<div class="form-field recaptcha ">
|
||
|
||
|
||
|
||
<div class="g-recaptcha" id="id-recaptcha" data-sitekey="6LfsWHMdAAAAAClKbtOpjQ2pMjgsGxvv7NdZW9uI"></div>
|
||
|
||
|
||
|
||
|
||
|
||
</div>
|
||
<div id="captcha-error-message" class="usa-input-error-message captcha-validation-message" role="alert"></div>
|
||
|
||
|
||
|
||
<div class="action-panel-actions">
|
||
<button class="action-panel-submit"
|
||
type="submit"
|
||
data-loading-label="Sending..."
|
||
data-ga-category="save_share"
|
||
data-ga-action="email"
|
||
data-ga-label="send">
|
||
Send email
|
||
</button>
|
||
<button class="action-panel-cancel"
|
||
aria-label="Close 'Email citations' panel"
|
||
ref="linksrc=close_email_panel"
|
||
aria-controls="email-action-panel"
|
||
aria-expanded="false"
|
||
data-ga-category="save_share"
|
||
data-ga-action="email"
|
||
data-ga-label="cancel">
|
||
Cancel
|
||
</button>
|
||
</div>
|
||
<input type="hidden" name="email-search-details" value="" />
|
||
<input type="hidden" name="email-search-details-hash" value="0e42663a6c3bd85498fcb88798998fed7bfdc45d457db35281e41afe13cc0524" />
|
||
</form>
|
||
</div>
|
||
</div>
|
||
|
||
<div id="collections-action-panel"
|
||
class="collections-action-panel action-panel in-progress-dots-panel"
|
||
aria-hidden="true"
|
||
data-collections-open-panel-enabled="false"
|
||
data-collections-open-panel-url-hash="#open-collections-panel">
|
||
<div class="inner-wrap">
|
||
<h3 class="action-panel-heading">
|
||
Add to Collections
|
||
</h3>
|
||
|
||
|
||
<form id="collections-action-panel-form"
|
||
class="collections-action-panel-form action-panel-content action-form action-panel-smaller-selectors"
|
||
data-existing-collections-url="/list-existing-collections/"
|
||
data-add-to-existing-collection-url="/add-to-existing-collection/"
|
||
data-create-and-add-to-new-collection-url="/create-and-add-to-new-collection/"
|
||
data-get-article-ids-by-search-url="/get-article-ids-by-search/"
|
||
data-myncbi-max-collection-name-length="100"
|
||
data-add-to-collection-max-amount="1000"
|
||
data-collections-root-url="https://www.ncbi.nlm.nih.gov/myncbi/collections/">
|
||
|
||
<input type="hidden" name="csrfmiddlewaretoken" value="sr59QRamzDy1XqCXGhVRUiVkDuRmLGScJePetHDI9elvRRINjAyToqrYbyzyEhqw">
|
||
|
||
|
||
|
||
<div class="choice-group" role="radiogroup">
|
||
<ul class="radio-group-items">
|
||
<li>
|
||
<input type="radio"
|
||
id="collections-action-panel-new"
|
||
class="collections-new"
|
||
name="collections"
|
||
value="new"
|
||
data-ga-category="save_share"
|
||
data-ga-action="collections"
|
||
data-ga-label="collections_radio_new">
|
||
<label for="collections-action-panel-new">Create a new collection</label>
|
||
</li>
|
||
<li>
|
||
<input type="radio"
|
||
id="collections-action-panel-existing"
|
||
class="collections-existing"
|
||
name="collections"
|
||
value="existing"
|
||
checked="true"
|
||
data-ga-category="save_share"
|
||
data-ga-action="collections"
|
||
data-ga-label="collections_radio_existing">
|
||
<label for="collections-action-panel-existing">Add to an existing collection</label>
|
||
</li>
|
||
</ul>
|
||
</div>
|
||
|
||
<div class="controls-wrapper">
|
||
<div class="action-panel-control-wrap new-collections-controls">
|
||
<label for="collections-action-panel-add-to-new" class="action-panel-label required-field-asterisk">
|
||
Name your collection:
|
||
</label>
|
||
<input
|
||
type="text"
|
||
name="add-to-new-collection"
|
||
id="collections-action-panel-add-to-new"
|
||
class="collections-action-add-to-new"
|
||
pattern="[^"&=<>\/]*" title="The following characters are not allowed in the Name field: "&=<>/"
|
||
maxlength="100"
|
||
data-ga-category="save_share"
|
||
data-ga-action="create_collection"
|
||
data-ga-label="non_favorties_collection">
|
||
<div class="collections-new-name-too-long usa-input-error-message selection-validation-message">
|
||
Name must be less than 100 characters
|
||
</div>
|
||
</div>
|
||
<div class="action-panel-control-wrap existing-collections-controls">
|
||
<label for="collections-action-panel-add-to-existing" class="action-panel-label">
|
||
Choose a collection:
|
||
</label>
|
||
<select id="collections-action-panel-add-to-existing"
|
||
class="action-panel-selector collections-action-add-to-existing"
|
||
data-ga-category="save_share"
|
||
data-ga-action="select_collection"
|
||
data-ga-label="($('#collections-action-add-to-existing').val() === 'Favorites') ? 'Favorites' : 'non_favorites_collection'">
|
||
</select>
|
||
<div class="collections-retry-load-on-error usa-input-error-message selection-validation-message">
|
||
Unable to load your collection due to an error<br>
|
||
<a href="#">Please try again</a>
|
||
</div>
|
||
</div>
|
||
</div>
|
||
|
||
<div class="action-panel-actions">
|
||
<button class="action-panel-submit"
|
||
type="submit"
|
||
data-loading-label="Adding..."
|
||
data-pinger-ignore
|
||
data-ga-category="save_share"
|
||
data-ga-action="collections"
|
||
data-ga-label="add">
|
||
Add
|
||
</button>
|
||
<button class="action-panel-cancel"
|
||
aria-label="Close 'Add to Collections' panel"
|
||
ref="linksrc=close_collections_panel"
|
||
aria-controls="collections-action-panel"
|
||
aria-expanded="false"
|
||
data-ga-category="save_share"
|
||
data-ga-action="collections"
|
||
data-ga-label="cancel">
|
||
Cancel
|
||
</button>
|
||
</div>
|
||
</form>
|
||
</div>
|
||
</div>
|
||
|
||
<div id="bibliography-action-panel"
|
||
class="bibliography-action-panel action-panel in-progress-dots-panel"
|
||
aria-hidden="true"
|
||
data-bibliography-open-panel-enabled="false"
|
||
data-bibliography-open-panel-url-hash="#open-bibliography-panel">
|
||
<div class="inner-wrap">
|
||
<h3 class="action-panel-heading">
|
||
Add to My Bibliography
|
||
</h3>
|
||
<form id="bibliography-action-panel-form"
|
||
class="bibliography-action-panel-form action-panel-content action-form action-panel-smaller-selectors"
|
||
data-add-to-bibliography-max-amount="100"
|
||
data-add-to-bibliography-batch-size="10"
|
||
data-bibliography-delegates-url="/list-bibliography-delegates/"
|
||
data-add-to-bibliography-url="/add-to-bibliography/"
|
||
data-get-article-ids-by-search-url="/get-article-ids-by-search/"
|
||
data-mybib-root-url="https://www.ncbi.nlm.nih.gov/myncbi/collections/mybibliography/">
|
||
|
||
<input type="hidden" name="csrfmiddlewaretoken" value="sr59QRamzDy1XqCXGhVRUiVkDuRmLGScJePetHDI9elvRRINjAyToqrYbyzyEhqw">
|
||
|
||
|
||
|
||
<div class="action-panel-control-wrap bibliographies-controls">
|
||
<div class="choice-group">
|
||
<ul class="bibliographies-action-add radio-group-items">
|
||
<li>
|
||
<input name="bibliography" id="my-bibliography" class="my-bibliography" type="radio" checked/>
|
||
<label for="my-bibliography">My Bibliography</label>
|
||
</li>
|
||
</ul>
|
||
</div>
|
||
</div>
|
||
|
||
<div class="bibliographies-retry-load-on-error usa-input-error-message selection-validation-message">
|
||
Unable to load your delegates due to an error<br>
|
||
<a href="#">Please try again</a>
|
||
</div>
|
||
|
||
<div class="action-panel-actions">
|
||
<button class="action-panel-submit"
|
||
type="submit"
|
||
data-loading-label="Adding..."
|
||
data-pinger-ignore>
|
||
Add
|
||
</button>
|
||
<button class="action-panel-cancel"
|
||
aria-label="Close 'Add to bibliography' panel"
|
||
ref="linksrc=close_bibliography_panel"
|
||
aria-controls="bibliography-action-panel"
|
||
aria-expanded="false"
|
||
data-ga-category="save_share"
|
||
data-ga-action="mybib"
|
||
data-ga-label="cancel">
|
||
Cancel
|
||
</button>
|
||
</div>
|
||
</form>
|
||
</div>
|
||
</div>
|
||
|
||
|
||
|
||
|
||
<div id="saved-search-action-panel" class="saved-search-action-panel action-panel " aria-hidden="true"
|
||
data-saved-search-open-panel-enabled="false"
|
||
data-saved-search-open-panel-url-hash="#open-saved-search-panel">
|
||
<div class="inner-wrap">
|
||
<h2 class="action-panel-heading">
|
||
Your saved search
|
||
</h2>
|
||
|
||
<form id="saved-search-action-panel-form"
|
||
class="saved-search-action-panel-form action-panel-content action-form"
|
||
data-create-saved-search-url="/create-saved-search/"
|
||
data-try-search-terms-url="/try-search-term/"
|
||
data-saved-search-root-url="https://www.ncbi.nlm.nih.gov/myncbi/searches/">
|
||
|
||
<input type="hidden" name="csrfmiddlewaretoken" value="sr59QRamzDy1XqCXGhVRUiVkDuRmLGScJePetHDI9elvRRINjAyToqrYbyzyEhqw">
|
||
|
||
<div class="action-panel-control-wrap">
|
||
<label for="saved-search-name" class="action-panel-label saved-search-name-label required-field-asterisk">
|
||
Name of saved search:
|
||
</label>
|
||
<input maxlength="200"
|
||
type="text"
|
||
name="saved-search-name"
|
||
id="saved-search-name"
|
||
class="saved-search-name"
|
||
value=""
|
||
required
|
||
pattern="[^"&=<>\/]*" title="The following characters are not allowed in the Name field: "&=<>/">
|
||
</div>
|
||
|
||
<div class="action-panel-control-wrap">
|
||
<label for="saved-search-term" class="action-panel-label required-field-asterisk">
|
||
Search terms:
|
||
</label>
|
||
<textarea name="saved-search-term" id="saved-search-term" class="saved-search-term" required></textarea>
|
||
</div>
|
||
<div class="test-search-term-wrap">
|
||
<a href="#" class="try-search-term">Test search terms</a>
|
||
</div>
|
||
<div class="choice-group action-panel-extra-margin-top">
|
||
<span class="action-panel-label" id="fieldset-label">
|
||
Would you like email updates of new search results?
|
||
</span>
|
||
<fieldset id="saved-search-alert" aria-describedby="fieldset-label">
|
||
<legend class="usa-sr-only">Saved Search Alert Radio Buttons</legend>
|
||
<ul class="radio-group-items">
|
||
<li>
|
||
<input type="radio" id="saved-search-alert-yes" class="saved-search-alert-yes" name="saved-search-alert" value="yes" checked>
|
||
<label for="saved-search-alert-yes" class="action-panel-label">Yes</label>
|
||
</li>
|
||
<li>
|
||
<input aria-label="No radio input" type="radio" id="saved-search-alert-no" class="saved-search-alert-no" name="saved-search-alert" value="no">
|
||
<label for="saved-search-alert-no" class="action-panel-label">No</label>
|
||
</li>
|
||
</ul>
|
||
</fieldset>
|
||
</div>
|
||
|
||
<div class="alert-schedule-wrap">
|
||
<div class="action-panel-control-wrap">
|
||
<label class="action-panel-label">
|
||
Email:
|
||
</label>
|
||
<span aria-label="Email address" id="saved-search-email" class="action-panel-label"><span class="action-panel-label-bold"></span> (<a class="myncbi-account-settings" href="https://www.ncbi.nlm.nih.gov/account/settings/">change</a>)</span>
|
||
</div>
|
||
<div class="action-panel-control-wrap action-panel-extra-margin-top">
|
||
<label for="saved-search-frequency" class="action-panel-label">
|
||
Frequency:
|
||
</label>
|
||
<select id="saved-search-frequency" class="no-border-panel-selector saved-search-frequency">
|
||
<option value="monthly">Monthly</option>
|
||
<option value="weekly">Weekly</option>
|
||
<option value="daily">Daily</option>
|
||
</select>
|
||
</div>
|
||
<div class="action-panel-control-wrap saved-search-monthly-additional">
|
||
<label for="saved-search-monthly-on-day" class="action-panel-label">
|
||
Which day?
|
||
</label>
|
||
<select id="saved-search-monthly-on-day" class="no-border-panel-selector">
|
||
<option value="Sunday">The first Sunday</option>
|
||
<option value="Monday">The first Monday</option>
|
||
<option value="Tuesday">The first Tuesday</option>
|
||
<option value="Wednesday">The first Wednesday</option>
|
||
<option value="Thursday">The first Thursday</option>
|
||
<option value="Friday">The first Friday</option>
|
||
<option value="Saturday">The first Saturday</option>
|
||
<option value="day">The first day</option>
|
||
<option value="weekday">The first weekday</option>
|
||
</select>
|
||
</div>
|
||
<div class="action-panel-control-wrap saved-search-weekly-additional">
|
||
<label for="saved-search-weekly-on-day" class="action-panel-label">
|
||
Which day?
|
||
</label>
|
||
<select id="saved-search-weekly-on-day" class="no-border-panel-selector saved-search-weekly-on-day">
|
||
<option value="Sunday">Sunday</option>
|
||
<option value="Monday">Monday</option>
|
||
<option value="Tuesday">Tuesday</option>
|
||
<option value="Wednesday">Wednesday</option>
|
||
<option value="Thursday">Thursday</option>
|
||
<option value="Friday">Friday</option>
|
||
<option value="Saturday">Saturday</option>
|
||
</select>
|
||
</div>
|
||
<div class="action-panel-control-wrap">
|
||
<label for="saved-search-report" class="action-panel-label">
|
||
Report format:
|
||
</label>
|
||
<select id="saved-search-report" class="no-border-panel-selector saved-search-report">
|
||
<option value="DocSum">Summary</option>
|
||
<option value="DocSumText">Summary (text)</option>
|
||
<option value="Abstract">Abstract</option>
|
||
<option value="AbstractText">Abstract (text)</option>
|
||
<option value="MEDLINE">PubMed</option>
|
||
</select>
|
||
</div>
|
||
<div class="action-panel-control-wrap">
|
||
<label for="saved-search-amount" class="action-panel-label">
|
||
Send at most:
|
||
</label>
|
||
<select id="saved-search-amount" class="no-border-panel-selector saved-search-amount">
|
||
<option value="1">1 item</option>
|
||
<option value="5" selected>5 items</option>
|
||
<option value="10">10 items</option>
|
||
<option value="20">20 items</option>
|
||
<option value="50">50 items</option>
|
||
<option value="100">100 items</option>
|
||
<option value="200">200 items</option>
|
||
</select>
|
||
</div>
|
||
<div>
|
||
<input type="checkbox" id="saved-search-send-if-no-result" class="saved-search-send-if-no-result" name="saved-search-send-if-no-result">
|
||
<label for="saved-search-send-if-no-result" class="action-panel-label smaller-checkbox">
|
||
Send even when there aren't any new results
|
||
</label>
|
||
</div>
|
||
<div class="action-panel-control-wrap option-text-in-email-wrap">
|
||
<label for="saved-search-email-text" class="action-panel-label">
|
||
Optional text in email:
|
||
</label>
|
||
<textarea name="saved-search-email-text"
|
||
id="saved-search-email-text"
|
||
class="saved-search-email-text"></textarea>
|
||
</div>
|
||
|
||
</div>
|
||
|
||
<div class="action-panel-actions">
|
||
<button class="action-panel-submit"
|
||
type="submit"
|
||
data-loading-label="Saving..."
|
||
data-ga-category="save_share"
|
||
data-ga-action="alert"
|
||
data-ga-label="save">
|
||
Save
|
||
</button>
|
||
<button class="action-panel-cancel"
|
||
aria-label="Close 'Your saved search' panel"
|
||
ref="linksrc=close_saved_search_panel"
|
||
aria-controls="saved-search-action-panel"
|
||
aria-expanded="false"
|
||
data-ga-category="save_share"
|
||
data-ga-action="alert"
|
||
data-ga-label="cancel">
|
||
Cancel
|
||
</button>
|
||
</div>
|
||
</form>
|
||
</div>
|
||
</div>
|
||
|
||
<div id="citation-manager-action-panel" class="citation-manager-action-panel action-panel" aria-hidden="true">
|
||
<div class="inner-wrap">
|
||
<h2 class="action-panel-heading">
|
||
Create a file for external citation management software
|
||
</h2>
|
||
<form id="citation-manager-action-panel-form"
|
||
class="action-panel-content action-form"
|
||
action="/results-export-ids/"
|
||
data-by-search-action="/results-export-search-data/"
|
||
data-by-ids-action="/results-export-ids/"
|
||
method="post"
|
||
data-by-search-method="post"
|
||
data-by-ids-method="post">
|
||
|
||
<input type="hidden" name="csrfmiddlewaretoken" value="sr59QRamzDy1XqCXGhVRUiVkDuRmLGScJePetHDI9elvRRINjAyToqrYbyzyEhqw">
|
||
|
||
|
||
|
||
<input name="results-format" type="hidden" value="pubmed"/>
|
||
|
||
<div class="action-panel-actions">
|
||
<button class="action-panel-submit"
|
||
type="submit"
|
||
data-loading-label="Sending..."
|
||
data-ga-category="save_share"
|
||
data-ga-action="citation_manager"
|
||
data-ga-label="save">
|
||
Create file
|
||
</button>
|
||
<button class="action-panel-cancel"
|
||
aria-label="Close 'Send citations to citation manager' panel"
|
||
ref="linksrc=close_citation_manager_panel"
|
||
aria-controls="citation-manager-action-panel"
|
||
aria-expanded="false"
|
||
data-ga-category="save_share"
|
||
data-ga-action="citation_manager"
|
||
data-ga-label="cancel">
|
||
Cancel
|
||
</button>
|
||
</div>
|
||
</form>
|
||
</div>
|
||
</div>
|
||
|
||
|
||
|
||
|
||
<div id="rss-action-panel" class="rss-action-panel action-panel " aria-hidden="true">
|
||
<div class="inner-wrap">
|
||
<h2 class="action-panel-heading">
|
||
Your RSS Feed
|
||
</h2>
|
||
|
||
<form id="rss-action-panel-form"
|
||
class="rss-action-panel-form action-panel-content action-form"
|
||
data-create-rss-feed-url="/create-rss-feed-url/"
|
||
data-search-form-term-value="">
|
||
|
||
<input type="hidden" name="csrfmiddlewaretoken" value="sr59QRamzDy1XqCXGhVRUiVkDuRmLGScJePetHDI9elvRRINjAyToqrYbyzyEhqw">
|
||
|
||
<div class="action-panel-control-wrap">
|
||
<label for="rss-name" class="action-panel-label required-field-asterisk">
|
||
Name of RSS Feed:
|
||
</label>
|
||
<input maxlength="200"
|
||
placeholder="Name"
|
||
type="text"
|
||
name="rss-name"
|
||
id="rss-name"
|
||
class="rss-name"
|
||
value=''
|
||
required
|
||
pattern="[^"&=<>\/]*" title="The following characters are not allowed in the Name field: "&=<>/">
|
||
</div>
|
||
|
||
<div class="rss-limit-wrap">
|
||
<div class="action-panel-control-wrap action-panel-extra-margin-top">
|
||
<label for="rss-limit" class="action-panel-label">
|
||
Number of items displayed:
|
||
</label>
|
||
<select id="rss-limit" class="no-border-panel-selector rss-limit">
|
||
<option value="5">5</option>
|
||
<option value="10">10</option>
|
||
<option value="15" selected="selected">15</option>
|
||
<option value="20">20</option>
|
||
<option value="50">50</option>
|
||
<option value="100">100</option>
|
||
</select>
|
||
</div>
|
||
</div>
|
||
|
||
<div class="action-panel-actions">
|
||
<button class="action-panel-submit"
|
||
type="submit"
|
||
data-loading-label="Creating..."
|
||
data-ga-category="save_share"
|
||
data-ga-action="alert"
|
||
data-ga-label="save">
|
||
Create RSS
|
||
</button>
|
||
<button class="action-panel-cancel"
|
||
aria-label="Close 'Your RSS' panel"
|
||
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</a></li></ul></div></div></div><span class="period">. </span><span class="cit">2024 Sep;23(9):913-924.</span>
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<span class="citation-doi">
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<span class="secondary-date">
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Epub 2024 Jul 26.
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<h1 class="heading-title">
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γ-Secretase activity, clinical features, and biomarkers of autosomal dominant Alzheimer's disease: cross-sectional and longitudinal analysis of the Dominantly Inherited Alzheimer Network observational study (DIAN-OBS)
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<div class="extended-article-details" id="expanded-authors" aria-hidden="true">
|
||
|
||
|
||
|
||
|
||
<div class="expanded-authors" id="full-view-expanded-authors">
|
||
|
||
|
||
|
||
|
||
|
||
|
||
|
||
|
||
|
||
<div class="collaborations">
|
||
<h3 class="title">
|
||
|
||
Collaborators
|
||
|
||
</h3>
|
||
<ul class="group-list">
|
||
|
||
<li>
|
||
|
||
<strong class="title">Dominantly Inherited Alzheimer Network</strong>:
|
||
|
||
|
||
|
||
|
||
<div class="authors-list">
|
||
<span class="authors-list-item "><a class="full-name"
|
||
href="/?term=Aguillon+D"
|
||
ref="linksrc=author_name_link"
|
||
data-ga-category="search"
|
||
data-ga-action="author_link"
|
||
data-ga-label="David Aguillon">David Aguillon</a><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name"
|
||
href="/?term=Allegri+RF"
|
||
ref="linksrc=author_name_link"
|
||
data-ga-category="search"
|
||
data-ga-action="author_link"
|
||
data-ga-label="Ricardo F Allegri">Ricardo F Allegri</a><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name"
|
||
href="/?term=Aschenbrenner+AJ"
|
||
ref="linksrc=author_name_link"
|
||
data-ga-category="search"
|
||
data-ga-action="author_link"
|
||
data-ga-label="Andrew J Aschenbrenner">Andrew J Aschenbrenner</a><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name"
|
||
href="/?term=Baker+B"
|
||
ref="linksrc=author_name_link"
|
||
data-ga-category="search"
|
||
data-ga-action="author_link"
|
||
data-ga-label="Bryce Baker">Bryce Baker</a><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name"
|
||
href="/?term=Barthelemy+N"
|
||
ref="linksrc=author_name_link"
|
||
data-ga-category="search"
|
||
data-ga-action="author_link"
|
||
data-ga-label="Nicolas Barthelemy">Nicolas Barthelemy</a><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name"
|
||
href="/?term=Bechara+JA"
|
||
ref="linksrc=author_name_link"
|
||
data-ga-category="search"
|
||
data-ga-action="author_link"
|
||
data-ga-label="Jacob A Bechara">Jacob A Bechara</a><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name"
|
||
href="/?term=Berman+SB"
|
||
ref="linksrc=author_name_link"
|
||
data-ga-category="search"
|
||
data-ga-action="author_link"
|
||
data-ga-label="Sarah B Berman">Sarah B Berman</a><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name"
|
||
href="/?term=Brooks+WS"
|
||
ref="linksrc=author_name_link"
|
||
data-ga-category="search"
|
||
data-ga-action="author_link"
|
||
data-ga-label="William S Brooks">William S Brooks</a><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name"
|
||
href="/?term=Cash+DM"
|
||
ref="linksrc=author_name_link"
|
||
data-ga-category="search"
|
||
data-ga-action="author_link"
|
||
data-ga-label="David M Cash">David M Cash</a><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name"
|
||
href="/?term=Chen+A"
|
||
ref="linksrc=author_name_link"
|
||
data-ga-category="search"
|
||
data-ga-action="author_link"
|
||
data-ga-label="Allison Chen">Allison Chen</a><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name"
|
||
href="/?term=Chrem+Mendez+P"
|
||
ref="linksrc=author_name_link"
|
||
data-ga-category="search"
|
||
data-ga-action="author_link"
|
||
data-ga-label="Patricio Chrem Mendez">Patricio Chrem Mendez</a><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name"
|
||
href="/?term=Courtney+L"
|
||
ref="linksrc=author_name_link"
|
||
data-ga-category="search"
|
||
data-ga-action="author_link"
|
||
data-ga-label="Laura Courtney">Laura Courtney</a><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name"
|
||
href="/?term=Cruchaga+C"
|
||
ref="linksrc=author_name_link"
|
||
data-ga-category="search"
|
||
data-ga-action="author_link"
|
||
data-ga-label="Carlos Cruchaga">Carlos Cruchaga</a><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name"
|
||
href="/?term=Daniels+AJ"
|
||
ref="linksrc=author_name_link"
|
||
data-ga-category="search"
|
||
data-ga-action="author_link"
|
||
data-ga-label="Alisha J Daniels">Alisha J Daniels</a><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name"
|
||
href="/?term=Fagan+AM"
|
||
ref="linksrc=author_name_link"
|
||
data-ga-category="search"
|
||
data-ga-action="author_link"
|
||
data-ga-label="Anne M Fagan">Anne M Fagan</a><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name"
|
||
href="/?term=Flores+S"
|
||
ref="linksrc=author_name_link"
|
||
data-ga-category="search"
|
||
data-ga-action="author_link"
|
||
data-ga-label="Shaney Flores">Shaney Flores</a><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name"
|
||
href="/?term=Fox+NC"
|
||
ref="linksrc=author_name_link"
|
||
data-ga-category="search"
|
||
data-ga-action="author_link"
|
||
data-ga-label="Nick C Fox">Nick C Fox</a><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name"
|
||
href="/?term=Franklin+E"
|
||
ref="linksrc=author_name_link"
|
||
data-ga-category="search"
|
||
data-ga-action="author_link"
|
||
data-ga-label="Erin Franklin">Erin Franklin</a><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name"
|
||
href="/?term=Goate+AM"
|
||
ref="linksrc=author_name_link"
|
||
data-ga-category="search"
|
||
data-ga-action="author_link"
|
||
data-ga-label="Alison M Goate">Alison M Goate</a><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name"
|
||
href="/?term=Graber-Sultan+S"
|
||
ref="linksrc=author_name_link"
|
||
data-ga-category="search"
|
||
data-ga-action="author_link"
|
||
data-ga-label="Susanne Graber-Sultan">Susanne Graber-Sultan</a><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name"
|
||
href="/?term=Graff-Radford+NR"
|
||
ref="linksrc=author_name_link"
|
||
data-ga-category="search"
|
||
data-ga-action="author_link"
|
||
data-ga-label="Neill R Graff-Radford">Neill R Graff-Radford</a><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name"
|
||
href="/?term=Gremminger+E"
|
||
ref="linksrc=author_name_link"
|
||
data-ga-category="search"
|
||
data-ga-action="author_link"
|
||
data-ga-label="Emily Gremminger">Emily Gremminger</a><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name"
|
||
href="/?term=Herries+E"
|
||
ref="linksrc=author_name_link"
|
||
data-ga-category="search"
|
||
data-ga-action="author_link"
|
||
data-ga-label="Elizabeth Herries">Elizabeth Herries</a><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name"
|
||
href="/?term=Hofmann+A"
|
||
ref="linksrc=author_name_link"
|
||
data-ga-category="search"
|
||
data-ga-action="author_link"
|
||
data-ga-label="Anna Hofmann">Anna Hofmann</a><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name"
|
||
href="/?term=Holtzman+DM"
|
||
ref="linksrc=author_name_link"
|
||
data-ga-category="search"
|
||
data-ga-action="author_link"
|
||
data-ga-label="David M Holtzman">David M Holtzman</a><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name"
|
||
href="/?term=Hornbeck+R"
|
||
ref="linksrc=author_name_link"
|
||
data-ga-category="search"
|
||
data-ga-action="author_link"
|
||
data-ga-label="Russ Hornbeck">Russ Hornbeck</a><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name"
|
||
href="/?term=Huey+ED"
|
||
ref="linksrc=author_name_link"
|
||
data-ga-category="search"
|
||
data-ga-action="author_link"
|
||
data-ga-label="Edward D Huey">Edward D Huey</a><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name"
|
||
href="/?term=Ibanez+L"
|
||
ref="linksrc=author_name_link"
|
||
data-ga-category="search"
|
||
data-ga-action="author_link"
|
||
data-ga-label="Laura Ibanez">Laura Ibanez</a><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name"
|
||
href="/?term=Ikeuchi+T"
|
||
ref="linksrc=author_name_link"
|
||
data-ga-category="search"
|
||
data-ga-action="author_link"
|
||
data-ga-label="Takeshi Ikeuchi">Takeshi Ikeuchi</a><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name"
|
||
href="/?term=Ikonomovic+S"
|
||
ref="linksrc=author_name_link"
|
||
data-ga-category="search"
|
||
data-ga-action="author_link"
|
||
data-ga-label="Snezana Ikonomovic">Snezana Ikonomovic</a><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name"
|
||
href="/?term=Jackson+K"
|
||
ref="linksrc=author_name_link"
|
||
data-ga-category="search"
|
||
data-ga-action="author_link"
|
||
data-ga-label="Kelley Jackson">Kelley Jackson</a><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name"
|
||
href="/?term=Jarman+S"
|
||
ref="linksrc=author_name_link"
|
||
data-ga-category="search"
|
||
data-ga-action="author_link"
|
||
data-ga-label="Steve Jarman">Steve Jarman</a><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name"
|
||
href="/?term=Jerome+G"
|
||
ref="linksrc=author_name_link"
|
||
data-ga-category="search"
|
||
data-ga-action="author_link"
|
||
data-ga-label="Gina Jerome">Gina Jerome</a><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name"
|
||
href="/?term=Johnson+ECB"
|
||
ref="linksrc=author_name_link"
|
||
data-ga-category="search"
|
||
data-ga-action="author_link"
|
||
data-ga-label="Erik C B Johnson">Erik C B Johnson</a><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name"
|
||
href="/?term=Kasuga+K"
|
||
ref="linksrc=author_name_link"
|
||
data-ga-category="search"
|
||
data-ga-action="author_link"
|
||
data-ga-label="Kensaku Kasuga">Kensaku Kasuga</a><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name"
|
||
href="/?term=Keefe+S"
|
||
ref="linksrc=author_name_link"
|
||
data-ga-category="search"
|
||
data-ga-action="author_link"
|
||
data-ga-label="Sarah Keefe">Sarah Keefe</a><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name"
|
||
href="/?term=Koudelis+D"
|
||
ref="linksrc=author_name_link"
|
||
data-ga-category="search"
|
||
data-ga-action="author_link"
|
||
data-ga-label="Deborah Koudelis">Deborah Koudelis</a><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name"
|
||
href="/?term=Kuder-Buletta+E"
|
||
ref="linksrc=author_name_link"
|
||
data-ga-category="search"
|
||
data-ga-action="author_link"
|
||
data-ga-label="Elke Kuder-Buletta">Elke Kuder-Buletta</a><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name"
|
||
href="/?term=Laske+C"
|
||
ref="linksrc=author_name_link"
|
||
data-ga-category="search"
|
||
data-ga-action="author_link"
|
||
data-ga-label="Christoph Laske">Christoph Laske</a><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name"
|
||
href="/?term=Leon+YM"
|
||
ref="linksrc=author_name_link"
|
||
data-ga-category="search"
|
||
data-ga-action="author_link"
|
||
data-ga-label="Yudy Milena Leon">Yudy Milena Leon</a><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name"
|
||
href="/?term=Levey+AI"
|
||
ref="linksrc=author_name_link"
|
||
data-ga-category="search"
|
||
data-ga-action="author_link"
|
||
data-ga-label="Allan I Levey">Allan I Levey</a><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name"
|
||
href="/?term=Li+Y"
|
||
ref="linksrc=author_name_link"
|
||
data-ga-category="search"
|
||
data-ga-action="author_link"
|
||
data-ga-label="Yan Li">Yan Li</a><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name"
|
||
href="/?term=Llibre-Guerra+JJ"
|
||
ref="linksrc=author_name_link"
|
||
data-ga-category="search"
|
||
data-ga-action="author_link"
|
||
data-ga-label="Jorge J Llibre-Guerra">Jorge J Llibre-Guerra</a><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name"
|
||
href="/?term=Lopera+F"
|
||
ref="linksrc=author_name_link"
|
||
data-ga-category="search"
|
||
data-ga-action="author_link"
|
||
data-ga-label="Francisco Lopera">Francisco Lopera</a><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name"
|
||
href="/?term=Lu+R"
|
||
ref="linksrc=author_name_link"
|
||
data-ga-category="search"
|
||
data-ga-action="author_link"
|
||
data-ga-label="Ruijin Lu">Ruijin Lu</a><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name"
|
||
href="/?term=Marsh+J"
|
||
ref="linksrc=author_name_link"
|
||
data-ga-category="search"
|
||
data-ga-action="author_link"
|
||
data-ga-label="Jacob Marsh">Jacob Marsh</a><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name"
|
||
href="/?term=Martins+R"
|
||
ref="linksrc=author_name_link"
|
||
data-ga-category="search"
|
||
data-ga-action="author_link"
|
||
data-ga-label="Ralph Martins">Ralph Martins</a><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name"
|
||
href="/?term=Massoumzadeh+P"
|
||
ref="linksrc=author_name_link"
|
||
data-ga-category="search"
|
||
data-ga-action="author_link"
|
||
data-ga-label="Parinaz Massoumzadeh">Parinaz Massoumzadeh</a><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name"
|
||
href="/?term=Masters+C"
|
||
ref="linksrc=author_name_link"
|
||
data-ga-category="search"
|
||
data-ga-action="author_link"
|
||
data-ga-label="Colin Masters">Colin Masters</a><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name"
|
||
href="/?term=McCullough+A"
|
||
ref="linksrc=author_name_link"
|
||
data-ga-category="search"
|
||
data-ga-action="author_link"
|
||
data-ga-label="Austin McCullough">Austin McCullough</a><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name"
|
||
href="/?term=McKay+N"
|
||
ref="linksrc=author_name_link"
|
||
data-ga-category="search"
|
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data-ga-action="author_link"
|
||
data-ga-label="Nicole McKay">Nicole McKay</a><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name"
|
||
href="/?term=Minton+M"
|
||
ref="linksrc=author_name_link"
|
||
data-ga-category="search"
|
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data-ga-action="author_link"
|
||
data-ga-label="Matthew Minton">Matthew Minton</a><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name"
|
||
href="/?term=Mori+H"
|
||
ref="linksrc=author_name_link"
|
||
data-ga-category="search"
|
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data-ga-action="author_link"
|
||
data-ga-label="Hiroshi Mori">Hiroshi Mori</a><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name"
|
||
href="/?term=Morris+JC"
|
||
ref="linksrc=author_name_link"
|
||
data-ga-category="search"
|
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data-ga-action="author_link"
|
||
data-ga-label="John C Morris">John C Morris</a><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name"
|
||
href="/?term=Nadkarni+NK"
|
||
ref="linksrc=author_name_link"
|
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data-ga-category="search"
|
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data-ga-action="author_link"
|
||
data-ga-label="Neelesh K Nadkarni">Neelesh K Nadkarni</a><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name"
|
||
href="/?term=Nicklaus+J"
|
||
ref="linksrc=author_name_link"
|
||
data-ga-category="search"
|
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data-ga-action="author_link"
|
||
data-ga-label="Joyce Nicklaus">Joyce Nicklaus</a><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name"
|
||
href="/?term=Niimi+Y"
|
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ref="linksrc=author_name_link"
|
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data-ga-category="search"
|
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data-ga-action="author_link"
|
||
data-ga-label="Yoshiki Niimi">Yoshiki Niimi</a><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name"
|
||
href="/?term=Noble+JM"
|
||
ref="linksrc=author_name_link"
|
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data-ga-category="search"
|
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data-ga-action="author_link"
|
||
data-ga-label="James M Noble">James M Noble</a><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name"
|
||
href="/?term=Obermueller+U"
|
||
ref="linksrc=author_name_link"
|
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data-ga-category="search"
|
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data-ga-action="author_link"
|
||
data-ga-label="Ulrike Obermueller">Ulrike Obermueller</a><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name"
|
||
href="/?term=Picarello+DM"
|
||
ref="linksrc=author_name_link"
|
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data-ga-category="search"
|
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data-ga-action="author_link"
|
||
data-ga-label="Danielle M Picarello">Danielle M Picarello</a><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name"
|
||
href="/?term=Pulizos+C"
|
||
ref="linksrc=author_name_link"
|
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data-ga-category="search"
|
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data-ga-action="author_link"
|
||
data-ga-label="Christine Pulizos">Christine Pulizos</a><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name"
|
||
href="/?term=Ramirez+L"
|
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|
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PMID:
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<strong class="current-id" title="PubMed ID">39074479</strong>
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<span class="embargo-date-block">
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<div class="publication-type" >Observational Study</div>
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<h1 class="heading-title">
|
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|
||
|
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|
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|
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|
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|
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γ-Secretase activity, clinical features, and biomarkers of autosomal dominant Alzheimer's disease: cross-sectional and longitudinal analysis of the Dominantly Inherited Alzheimer Network observational study (DIAN-OBS)
|
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|
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|
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|
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</h1>
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<span class="authors-list-item "><span class="full-name">Stephanie A Schultz</span><span class="citation-separator"> et al.</span></span>
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Lancet Neurol<span class="citation-separator">.</span>
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</a></li></ul></div></div></div><span class="period">. </span><span class="cit">2024 Sep;23(9):913-924.</span>
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<span class="citation-doi">
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doi: 10.1016/S1474-4422(24)00236-9.
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<span class="secondary-date">
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Epub 2024 Jul 26.
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11
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<strong class="title">Dominantly Inherited Alzheimer Network</strong>:
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<h3 class="title">
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Affiliations
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<li data-affiliation-id="short-view-affiliation-1"
|
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id="short-view-affiliation-1"
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><sup class="key">1</sup> Department of Neurology, Massachusetts General Hospital, Boston, MA, USA; Department of Neurology, Medical School, Harvard University, Boston, MA, USA.</li>
|
||
|
||
<li data-affiliation-id="short-view-affiliation-2"
|
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id="short-view-affiliation-2"
|
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><sup class="key">2</sup> Department of Neurology, Brigham and Women's Hospital, Boston, MA, USA; Ann Romney Center for Neurologic Diseases, Boston, MA, USA.</li>
|
||
|
||
<li data-affiliation-id="short-view-affiliation-3"
|
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id="short-view-affiliation-3"
|
||
><sup class="key">3</sup> Department of Neurology, Massachusetts General Hospital, Boston, MA, USA; Department of Neurology, Medical School, Harvard University, Boston, MA, USA; Department of Neurology, Brigham and Women's Hospital, Boston, MA, USA.</li>
|
||
|
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<li data-affiliation-id="short-view-affiliation-4"
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id="short-view-affiliation-4"
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><sup class="key">4</sup> Mallinckrodt Institute of Radiology, Washington University, St Louis, MO, USA.</li>
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<li data-affiliation-id="short-view-affiliation-5"
|
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id="short-view-affiliation-5"
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><sup class="key">5</sup> Department of Neurology, Mayo Clinic, Jacksonville, FL, USA.</li>
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<li data-affiliation-id="short-view-affiliation-6"
|
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id="short-view-affiliation-6"
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><sup class="key">6</sup> Indiana Alzheimer's Disease Research Center, Indianapolis, IN, USA.</li>
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<li data-affiliation-id="short-view-affiliation-7"
|
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id="short-view-affiliation-7"
|
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><sup class="key">7</sup> Department of Psychology, Washington University, St Louis, MO, USA.</li>
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<li data-affiliation-id="short-view-affiliation-8"
|
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id="short-view-affiliation-8"
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><sup class="key">8</sup> Department of Neurology, Mayo Clinic, Rochester, MN, USA.</li>
|
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|
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<li data-affiliation-id="short-view-affiliation-9"
|
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id="short-view-affiliation-9"
|
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><sup class="key">9</sup> German Center for Neurodegenerative Diseases, Tübingen, Germany.</li>
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|
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<li data-affiliation-id="short-view-affiliation-10"
|
||
id="short-view-affiliation-10"
|
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><sup class="key">10</sup> Department of Psychiatry, Washington University, St Louis, MO, USA.</li>
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|
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<li data-affiliation-id="short-view-affiliation-11"
|
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id="short-view-affiliation-11"
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><sup class="key">11</sup> Department of Neurology, Asan Medical Center, College of Medicine, University of Ulsan, Seoul, South Korea.</li>
|
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|
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<li data-affiliation-id="short-view-affiliation-12"
|
||
id="short-view-affiliation-12"
|
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><sup class="key">12</sup> German Center for Neurodegenerative Diseases, Munich, Germany; Department of Neurology, Ludwig Maximilian University of Munich, Munich, Germany; Munich Cluster for Systems Neurology, Munich, Germany.</li>
|
||
|
||
<li data-affiliation-id="short-view-affiliation-13"
|
||
id="short-view-affiliation-13"
|
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><sup class="key">13</sup> Department of Psychiatry, Washington University, St Louis, MO, USA; Department of Pathology and Immunology, Washington University, St Louis, MO, USA.</li>
|
||
|
||
<li data-affiliation-id="short-view-affiliation-14"
|
||
id="short-view-affiliation-14"
|
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><sup class="key">14</sup> Neuroscience Research Australia, Randwick, NSW, Australia; School of Biomedical Sciences, University of New South Wales, Sydney, NSW, Australia.</li>
|
||
|
||
<li data-affiliation-id="short-view-affiliation-15"
|
||
id="short-view-affiliation-15"
|
||
><sup class="key">15</sup> Division of Biostatistics, Washington University, St Louis, MO, USA.</li>
|
||
|
||
<li data-affiliation-id="short-view-affiliation-16"
|
||
id="short-view-affiliation-16"
|
||
><sup class="key">16</sup> Department of Neurology, Washington University, St Louis, MO, USA.</li>
|
||
|
||
<li data-affiliation-id="short-view-affiliation-17"
|
||
id="short-view-affiliation-17"
|
||
><sup class="key">17</sup> Department of Neurology, Medical School, Harvard University, Boston, MA, USA; Department of Neurology, Brigham and Women's Hospital, Boston, MA, USA; Ann Romney Center for Neurologic Diseases, Boston, MA, USA.</li>
|
||
|
||
<li data-affiliation-id="short-view-affiliation-18"
|
||
id="short-view-affiliation-18"
|
||
><sup class="key">18</sup> Department of Neurology, Massachusetts General Hospital, Boston, MA, USA; Department of Neurology, Medical School, Harvard University, Boston, MA, USA; Department of Neurology, Brigham and Women's Hospital, Boston, MA, USA; Ann Romney Center for Neurologic Diseases, Boston, MA, USA. Electronic address: chhatwal.jasmeer@mgh.harvard.edu.</li>
|
||
|
||
</ul>
|
||
</div>
|
||
|
||
|
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|
||
|
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|
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<ul class="identifiers" id="short-view-identifiers">
|
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|
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<li>
|
||
<span class="identifier pubmed">
|
||
<span class="id-label">
|
||
|
||
PMID:
|
||
|
||
</span>
|
||
|
||
|
||
<strong class="current-id" title="PubMed ID">39074479</strong>
|
||
|
||
|
||
|
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</span>
|
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|
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|
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|
||
<span class="identifier pmc">
|
||
<span class="id-label">
|
||
|
||
PMCID:
|
||
|
||
</span>
|
||
|
||
|
||
<strong class="current-id" title="PMC ID">PMC11822357</strong>
|
||
|
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|
||
|
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<span class="embargo-date-block">
|
||
(available on
|
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<time
|
||
class="embargo-date" datetime="2025-09-01"
|
||
>2025-09-01</time>)
|
||
</span>
|
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|
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</span>
|
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|
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|
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|
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|
||
<span class="identifier doi">
|
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<span class="id-label">
|
||
|
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DOI:
|
||
|
||
</span>
|
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|
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|
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<a class="id-link"
|
||
target="_blank"
|
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rel="noopener"
|
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ref="linksrc=article_id_link&article_id=10.1016/S1474-4422(24)00236-9&id_type=DOI"
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href="https://doi.org/10.1016/s1474-4422(24)00236-9"
|
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|
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10.1016/S1474-4422(24)00236-9
|
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|
||
|
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|
||
|
||
</span>
|
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|
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<div class="abstract" id="abstract">
|
||
|
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<h2 class="title">
|
||
Abstract
|
||
|
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</h2>
|
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|
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|
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|
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<div class="abstract-content selected"
|
||
id="eng-abstract">
|
||
|
||
|
||
|
||
|
||
|
||
<p>
|
||
|
||
<strong class="sub-title">
|
||
Background:
|
||
</strong>
|
||
|
||
Genetic variants that cause autosomal dominant Alzheimer's disease are highly penetrant but vary substantially regarding age at symptom onset (AAO), rates of cognitive decline, and biomarker changes. Most pathogenic variants that cause autosomal dominant Alzheimer's disease are in presenilin 1 (PSEN1), which encodes the catalytic core of γ-secretase, an enzyme complex that is crucial in production of amyloid β. We aimed to investigate whether the heterogeneity in AAO and biomarker trajectories in carriers of PSEN1 pathogenic variants could be predicted on the basis of the effects of individual PSEN1 variants on γ-secretase activity and amyloid β production.
|
||
</p>
|
||
|
||
|
||
|
||
|
||
|
||
|
||
|
||
|
||
|
||
|
||
<p>
|
||
|
||
<strong class="sub-title">
|
||
Methods:
|
||
</strong>
|
||
|
||
For this cross-sectional and longitudinal analysis, we used data from participants enrolled in the Dominantly Inherited Alzheimer Network observational study (DIAN-OBS) via the DIAN-OBS data freeze version 15 (data collected between Feb 29, 2008, and June 30, 2020). The data freeze included data from 20 study sites in research institutions, universities, hospitals, and clinics across Europe, North and South America, Asia, and Oceania. We included individuals with PSEN1 pathogenic variants for whom relevant genetic, clinical, imaging, and CSF data were available. PSEN1 pathogenic variants were characterised via genetically modified PSEN1 and PSEN2 double-knockout human embryonic kidney 293T cells and immunoassays for Aβ37, Aβ38, Aβ40, Aβ42, and Aβ43. A summary measure of γ-secretase activity (γ-secretase composite [GSC]) was calculated for each variant and compared with clinical history-derived AAO using correlation analyses. We used linear mixed-effect models to assess associations between GSC scores and multimodal-biomarker and clinical data from DIAN-OBS. We used separate models to assess associations with Clinical Dementia Rating Sum of Boxes (CDR-SB), Mini-Mental State Examination (MMSE), and Wechsler Memory Scale-Revised (WMS-R) Logical Memory Delayed Recall, [<sup>11</sup>C]Pittsburgh compound B (PiB)-PET and brain glucose metabolism using [<sup>18</sup>F] fluorodeoxyglucose (FDG)-PET, CSF Aβ42-to-Aβ40 ratio (Aβ42/40), CSF log<sub>10</sub> (phosphorylated tau 181), CSF log<sub>10</sub> (phosphorylated tau 217), and MRI-based hippocampal volume.
|
||
</p>
|
||
|
||
|
||
|
||
|
||
|
||
|
||
|
||
|
||
|
||
|
||
<p>
|
||
|
||
<strong class="sub-title">
|
||
Findings:
|
||
</strong>
|
||
|
||
Data were included from 190 people carrying PSEN1 pathogenic variants, among whom median age was 39·0 years (IQR 32·0 to 48·0) and AAO was 44·5 years (40·6 to 51·4). 109 (57%) of 190 carriers were female and 81 (43%) were male. Lower GSC values (ie, lower γ-secretase activity than wild-type PSEN1) were associated with earlier AAO (r=0·58; p<0·0001). GSC was associated with MMSE (β=0·08, SE 0·03; p=0·0043), CDR-SB (-0·05, 0·02; p=0·0027), and WMS-R Logical Memory Delayed Recall scores (0·09, 0·02; p=0·0006). Lower GSC values were associated with faster increase in PiB-PET signal (p=0·0054), more rapid decreases in hippocampal volume (4·19, 0·77; p<0·0001), MMSE (0·02, 0·01; p=0·0020), and WMS-R Logical Memory Delayed Recall (0·004, 0·001; p=0·0003).
|
||
</p>
|
||
|
||
|
||
|
||
|
||
|
||
|
||
|
||
|
||
|
||
|
||
<p>
|
||
|
||
<strong class="sub-title">
|
||
Interpretation:
|
||
</strong>
|
||
|
||
Our findings suggest that clinical heterogeneity in people with autosomal dominant Alzheimer's disease can be at least partly explained by different effects of PSEN1 variants on γ-secretase activity and amyloid β production. They support targeting γ-secretase as a therapeutic approach and suggest that cell-based models could be used to improve prediction of symptom onset.
|
||
</p>
|
||
|
||
|
||
|
||
|
||
|
||
|
||
|
||
|
||
|
||
|
||
<p>
|
||
|
||
<strong class="sub-title">
|
||
Funding:
|
||
</strong>
|
||
|
||
US National Institute on Aging, Alzheimer's Association, German Center for Neurodegenerative Diseases, Raul Carrea Institute for Neurological Research, Japan Agency for Medical Research and Development, Korea Health Industry Development Institute, South Korean Ministry of Health and Welfare, South Korean Ministry of Science and ICT, and Spanish Institute of Health Carlos III.
|
||
</p>
|
||
|
||
|
||
|
||
|
||
|
||
|
||
</div>
|
||
|
||
|
||
|
||
|
||
|
||
|
||
|
||
|
||
|
||
|
||
|
||
</div>
|
||
|
||
|
||
|
||
|
||
|
||
|
||
<p class="copyright" id="copyright">
|
||
Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.
|
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</p>
|
||
|
||
|
||
<p class="disclaimer" id="disclaimer">
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<p xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:p1="http://pubmed.gov/pub-one">Declaration of interests SAS receives research funding from the Alzheimer's Association and the US National Institutes of Health (NIH). LL receives research funding from the US NIH; consulting fees from Korro Bio; and payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Biogen and Cell Signaling Technology. NJ-M receives research funding from the Alzheimer's Association and the US NIH. RJB receives research funding from the US NIH, Biogen, AbbVie, Bristol Myers Squibb, Novartis, the US National Intelligence Authority, US National Institute of Neurological Disorders and Stroke, Centene, the Rainwater Foundation, the BrightFocus Foundation, the Association for Frontotemporal Degeneration Biomarkers Initiative, Coins for Alzheimer's Research Trust Fund, the Good Ventures Foundation, Hoffman–La Roche, CogState, Signant, the Cure Alzheimer's Research Trust Fund, Eisai, and C2N Diagnostics; receives royalties or licences from C2N Diagnosticsf payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from the Korean Dementia Association, the American Neurological Association, Fondazione Prada, Weill Cornell Medical College, Harvard University, Beeson, and Adler Symposium. ZS receives research funding from the BrightFocus Foundation, the Foundation for Barnes-Jewish Hospital, Eli Lilly, the Health Equity Scholars Program, and the Alzheimer's Society of Canada. RAS receives research funding from the US NIH, the Gerald and Henrietta Rauenhorst Foundation, Eli Lilly, the Alzheimer's Assocation, and Eisai and receives consulting fees from AbbVie, Bristol Myers Squibb, Eisai, Eli Lilly, Roche, Prothena, AC Immune, Acumen, Alector, Alnylam, Biohaven, Genentech, Janssen, the Japanese Organization for Medical Device Development, Nervgen, Neuraly, Neurocentria, Oligomerix, Renew, Shionogi, Vigil Neuroscience, Ionis, and Vaxxinity. GSD receives research funcing from the US NIH, the Alzheimer's Association, and the Chan–Zuckerberg Initiative; consulting fees from Parabon Nanolabs and Arialysis Therapeutics; and payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from PeerView Media, Continuing Education, Eli Lilly, DynaMed, and SixSense Concierge. EM receives research funding from the US National Intelligence Authority, Eisai, Eli Lilly, Roche, and the Gerald and Henrietta Rauenhorst Foundation; consulting fees from AstraZeneca, Sanofi, and Merck; and payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from the Alzheimer Association, Projects in Knowledge, and Neurology Live. JPC receives research funding from the US NIH. RJP receives grants from the US NIH. JL is a consultant for and receives grants, contracts, and royalties from Eisai, Eli Lilly, the German Center of Neurodegenerative Diseases, the German Ministry for Research and Education, the Anton and Petra Ehrmann Foundation, the Luneburg Foundation, Innovationsfonds, the Michael J Fox Foundation, CurePSP, the Jerome LeJeune Foundation, the Alzheimer Forschungs Initiative, Deutsche Stiftung Down Syndrom, Else Kroner Fresenius Stiftung, and MODAG. DJS receives consulting fees from Prothena Biosciences and Eisai. CX receives research funding from the US NIH and consulting fees from Diadem. PRS receives research funding from the the US NIH, the Roth Charitable Foundation, the Australian National Health and Medical Research Council, and the Australian Medical Research Future Fund and receives consulting fees from Outside Opinion and Moira Clay Consulting. JJL receives research funding from the German Center for Neurodegenerative Diseases, the German Ministry for Research and Education, the Anton and Petra Ehrmann Foundation, the Lüneburg Foundation, Innovationsfonds, the Michael J Fox Foundation for Parkinson's Research, CurePSP, the Jerome LeJeune Foundation, the Alzheimer Forschungs Initiative, Deutsche Stiftung Down Syndrom, and Else Kröner Fresenius Stiftung; consulting fees from Eisai and Biogen; and payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Bayer Vital, Biogen, Eisai, Teva, Roche, and Zambon. MJ receives payment or honoraria for lectures, presentations, speakers, bureaus, manuscript writing, or educational events from Eisai. TLSB receives research funding from the US NIH and Siemens; consulting fees from Biogen, Eli Lilly, Eisai, Bristol Myers Squibb, and Johnson & Johnson; and payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Medscape and PeerView. All other authors declare no competing interests.</p>
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Lippa CF, Swearer JM, Kane KJ, et al. Familial Alzheimer’s disease: site of mutation influences clinical phenotype. Ann Neurol 2000; 48: 376–9.
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Lagomarsino VN, Pearse RV, Liu L, et al. Stem cell-derived neurons reflect features of protein networks, neuropathology, and cognitive outcome of their aged human donors. Neuron 2021; 109: 3402–3420.e9.
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Publication types
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class="keyword-actions-dropdown dropdown dropdown-container"
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aria-label="Dropdown menu for keyword Alzheimer Disease* / genetics"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link"
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href="/?term=%22Alzheimer+Disease%2Fgenetics%22%5BMAJR%5D&sort=date&sort_order=desc"
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data-href="/?term=%22Alzheimer+Disease%2Fgenetics%22%5BMAJR%5D&sort=date&sort_order=desc"
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Amyloid Precursor Protein Secretases* / metabolism
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aria-label="Dropdown menu for keyword Amyloid beta-Peptides* / cerebrospinal fluid"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link"
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href="/?term=%22Amyloid+beta-Peptides%2Fcerebrospinal+fluid%22%5BMAJR%5D&sort=date&sort_order=desc"
|
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data-href="/?term=%22Amyloid+beta-Peptides%2Fcerebrospinal+fluid%22%5BMAJR%5D&sort=date&sort_order=desc"
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Amyloid beta-Peptides* / metabolism
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hidden
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aria-label="Dropdown menu for keyword Amyloid beta-Peptides* / metabolism"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link"
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href="/?term=%22Amyloid+beta-Peptides%2Fmetabolism%22%5BMAJR%5D&sort=date&sort_order=desc"
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data-href="/?term=%22Amyloid+beta-Peptides%2Fmetabolism%22%5BMAJR%5D&sort=date&sort_order=desc"
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ref="linksrc=search_in_pubmed_keyword_link&mesh="Amyloid beta-Peptides/metabolism"[MAJR]"
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Search in PubMed
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</a></li><li><a class="search-in-mesh-link dropdown-block-link"
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Add to Search
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</a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link major"
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aria-label="Toggle dropdown menu for keyword Biomarkers* / cerebrospinal fluid"
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Biomarkers* / cerebrospinal fluid
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hidden
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href="/?term=%22Biomarkers%2Fcerebrospinal+fluid%22%5BMAJR%5D&sort=date&sort_order=desc"
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data-href="/?term=%22Biomarkers%2Fcerebrospinal+fluid%22%5BMAJR%5D&sort=date&sort_order=desc"
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ref="linksrc=search_in_pubmed_keyword_link&mesh="Biomarkers/cerebrospinal fluid"[MAJR]"
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Search in PubMed
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Search in MeSH
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</a></li><li><a class="add-to-search-link dropdown-block-link"
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data-search-term=""Biomarkers/cerebrospinal fluid"[MAJR]"
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Add to Search
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</a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link"
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aria-label="Toggle dropdown menu for keyword Cross-Sectional Studies"
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aria-expanded="false"
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data-pinger-ignore>
|
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Cross-Sectional Studies
|
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</button><div id="keyword-actions-mesh-terms-12"
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class="keyword-actions-dropdown dropdown dropdown-container"
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hidden
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aria-label="Dropdown menu for keyword Cross-Sectional Studies"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link"
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Search in MeSH
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|
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</button><div id="keyword-actions-mesh-terms-13"
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aria-label="Dropdown menu for keyword Female"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link"
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data-href="/?term=%22Female%22%5BMeSH%5D&sort=date&sort_order=desc"
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</a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link"
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Humans
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aria-label="Dropdown menu for keyword Humans"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link"
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</a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link"
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Longitudinal Studies
|
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|
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data-href="/?term=%22Longitudinal+Studies%22%5BMeSH%5D&sort=date&sort_order=desc"
|
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ref="linksrc=search_in_pubmed_keyword_link&mesh="Longitudinal Studies"[MeSH]"
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Search in MeSH
|
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</a></li><li><a class="add-to-search-link dropdown-block-link"
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data-search-term=""Longitudinal Studies"[MeSH]"
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data-ga-category="search"
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data-ga-action="add_to_search"
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data-ga-label=""Longitudinal Studies"[MeSH]"
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Add to Search
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</a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link"
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aria-label="Toggle dropdown menu for keyword Male"
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aria-expanded="false"
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Male
|
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</button><div id="keyword-actions-mesh-terms-16"
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class="keyword-actions-dropdown dropdown dropdown-container"
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hidden
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aria-label="Dropdown menu for keyword Male"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link"
|
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href="/?term=%22Male%22%5BMeSH%5D&sort=date&sort_order=desc"
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data-href="/?term=%22Male%22%5BMeSH%5D&sort=date&sort_order=desc"
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ref="linksrc=search_in_pubmed_keyword_link&mesh="Male"[MeSH]"
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Search in PubMed
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</a></li><li><a class="search-in-mesh-link dropdown-block-link"
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href="https://www.ncbi.nlm.nih.gov/mesh?term=Male"
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Search in MeSH
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</a></li><li><a class="add-to-search-link dropdown-block-link"
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data-search-term=""Male"[MeSH]"
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</a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link"
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Middle Aged
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</button><div id="keyword-actions-mesh-terms-17"
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class="keyword-actions-dropdown dropdown dropdown-container"
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aria-label="Dropdown menu for keyword Middle Aged"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link"
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href="/?term=%22Middle+Aged%22%5BMeSH%5D&sort=date&sort_order=desc"
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data-href="/?term=%22Middle+Aged%22%5BMeSH%5D&sort=date&sort_order=desc"
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ref="linksrc=search_in_pubmed_keyword_link&mesh="Middle Aged"[MeSH]"
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Search in PubMed
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data-ga-label=""Middle Aged"[MeSH]"
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</a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link major"
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aria-label="Toggle dropdown menu for keyword Presenilin-1* / genetics"
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Presenilin-1* / genetics
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</button><div id="keyword-actions-mesh-terms-major-18"
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hidden
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aria-label="Dropdown menu for keyword Presenilin-1* / genetics"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link"
|
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href="/?term=%22Presenilin-1%2Fgenetics%22%5BMAJR%5D&sort=date&sort_order=desc"
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data-href="/?term=%22Presenilin-1%2Fgenetics%22%5BMAJR%5D&sort=date&sort_order=desc"
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ref="linksrc=search_in_pubmed_keyword_link&mesh="Presenilin-1/genetics"[MAJR]"
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Search in PubMed
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|
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</a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link"
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aria-label="Toggle dropdown menu for keyword tau Proteins / cerebrospinal fluid"
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tau Proteins / cerebrospinal fluid
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</button><div id="keyword-actions-mesh-terms-19"
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hidden
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aria-label="Dropdown menu for keyword tau Proteins / cerebrospinal fluid"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link"
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href="/?term=%22tau+Proteins%2Fcerebrospinal+fluid%22%5BMeSH%5D&sort=date&sort_order=desc"
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data-href="/?term=%22tau+Proteins%2Fcerebrospinal+fluid%22%5BMeSH%5D&sort=date&sort_order=desc"
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ref="linksrc=search_in_pubmed_keyword_link&mesh="tau Proteins/cerebrospinal fluid"[MeSH]"
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Search in PubMed
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Add to Search
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</a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link"
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data-pinger-ignore>
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tau Proteins / genetics
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</button><div id="keyword-actions-mesh-terms-20"
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class="keyword-actions-dropdown dropdown dropdown-container"
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hidden
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aria-label="Dropdown menu for keyword tau Proteins / genetics"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link"
|
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href="/?term=%22tau+Proteins%2Fgenetics%22%5BMeSH%5D&sort=date&sort_order=desc"
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data-href="/?term=%22tau+Proteins%2Fgenetics%22%5BMeSH%5D&sort=date&sort_order=desc"
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ref="linksrc=search_in_pubmed_keyword_link&mesh="tau Proteins/genetics"[MeSH]"
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Search in PubMed
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</a></li><li><a class="search-in-mesh-link dropdown-block-link"
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Search in MeSH
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</a></li><li><a class="add-to-search-link dropdown-block-link"
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data-search-term=""tau Proteins/genetics"[MeSH]"
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data-ga-category="search"
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Add to Search
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</a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link"
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aria-label="Toggle dropdown menu for keyword tau Proteins / metabolism"
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tabindex="0"
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data-pinger-ignore>
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tau Proteins / metabolism
|
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</button><div id="keyword-actions-mesh-terms-21"
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class="keyword-actions-dropdown dropdown dropdown-container"
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hidden
|
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aria-label="Dropdown menu for keyword tau Proteins / metabolism"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link"
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href="/?term=%22tau+Proteins%2Fmetabolism%22%5BMeSH%5D&sort=date&sort_order=desc"
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data-href="/?term=%22tau+Proteins%2Fmetabolism%22%5BMeSH%5D&sort=date&sort_order=desc"
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ref="linksrc=search_in_pubmed_keyword_link&mesh="tau Proteins/metabolism"[MeSH]"
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Search in PubMed
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data-ga-action="mesh_term_link"
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Search in MeSH
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</a></li><li><a class="add-to-search-link dropdown-block-link"
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data-search-term=""tau Proteins/metabolism"[MeSH]"
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Add to Search
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</a></li></ul></div></div></div></li></ul>
|
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</div>
|
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|
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|
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|
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|
||
|
||
<div id="substances" class="substances keywords-section">
|
||
<h2 class="title">
|
||
Substances
|
||
</h2>
|
||
|
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<ul class="keywords-list"><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link"
|
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aria-label="Toggle dropdown menu for keyword Amyloid beta-Peptides"
|
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tabindex="0"
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aria-controls="keyword-actions-substances-0"
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aria-expanded="false"
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data-pinger-ignore>
|
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Amyloid beta-Peptides
|
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</button><div id="keyword-actions-substances-0"
|
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class="keyword-actions-dropdown dropdown dropdown-container"
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hidden
|
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aria-label="Dropdown menu for keyword Amyloid beta-Peptides"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link"
|
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href="/?term=%22Amyloid+beta-Peptides%22%5Bnm%5D&sort=date&sort_order=desc"
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data-href="/?term=%22Amyloid+beta-Peptides%22%5Bnm%5D&sort=date&sort_order=desc"
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ref="linksrc=search_in_pubmed_keyword_link&keyword="Amyloid beta-Peptides"[nm]"
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data-ga-category="search"
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data-ga-action="substance"
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data-ga-label="Amyloid beta-Peptides">
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Search in PubMed
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</a></li><li><a class="search-in-mesh-link dropdown-block-link"
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ref="linksrc=search_in_mesh_link"
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href="https://www.ncbi.nlm.nih.gov/mesh?term=%22Amyloid+beta-Peptides%22"
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data-ga-category="search_mesh"
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data-ga-action="substance_link"
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data-ga-label="Amyloid beta-Peptides">
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Search in MeSH
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</a></li><li><a class="add-to-search-link dropdown-block-link"
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ref="linksrc=add_to_search_link"
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role="button"
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data-search-term=""Amyloid beta-Peptides"[nm]"
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data-ga-category="search"
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data-ga-action="add_to_search"
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data-ga-label=""Amyloid beta-Peptides"[nm]"
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href="#">
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Add to Search
|
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</a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link"
|
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aria-label="Toggle dropdown menu for keyword Amyloid Precursor Protein Secretases"
|
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tabindex="0"
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aria-controls="keyword-actions-substances-1"
|
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aria-expanded="false"
|
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data-pinger-ignore>
|
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Amyloid Precursor Protein Secretases
|
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</button><div id="keyword-actions-substances-1"
|
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class="keyword-actions-dropdown dropdown dropdown-container"
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hidden
|
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aria-label="Dropdown menu for keyword Amyloid Precursor Protein Secretases"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link"
|
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href="/?term=%22Amyloid+Precursor+Protein+Secretases%22%5Bnm%5D&sort=date&sort_order=desc"
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data-href="/?term=%22Amyloid+Precursor+Protein+Secretases%22%5Bnm%5D&sort=date&sort_order=desc"
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ref="linksrc=search_in_pubmed_keyword_link&keyword="Amyloid Precursor Protein Secretases"[nm]"
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data-ga-category="search"
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data-ga-action="substance"
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data-ga-label="Amyloid Precursor Protein Secretases">
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Search in PubMed
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</a></li><li><a class="search-in-mesh-link dropdown-block-link"
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ref="linksrc=search_in_mesh_link"
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href="https://www.ncbi.nlm.nih.gov/mesh?term=%22Amyloid+Precursor+Protein+Secretases%22"
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data-ga-category="search_mesh"
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data-ga-action="substance_link"
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data-ga-label="Amyloid Precursor Protein Secretases">
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Search in MeSH
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</a></li><li><a class="add-to-search-link dropdown-block-link"
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ref="linksrc=add_to_search_link"
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role="button"
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data-search-term=""Amyloid Precursor Protein Secretases"[nm]"
|
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data-ga-category="search"
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data-ga-action="add_to_search"
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data-ga-label=""Amyloid Precursor Protein Secretases"[nm]"
|
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href="#">
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Add to Search
|
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</a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link"
|
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aria-label="Toggle dropdown menu for keyword Biomarkers"
|
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tabindex="0"
|
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aria-controls="keyword-actions-substances-2"
|
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aria-expanded="false"
|
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data-pinger-ignore>
|
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Biomarkers
|
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</button><div id="keyword-actions-substances-2"
|
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class="keyword-actions-dropdown dropdown dropdown-container"
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hidden
|
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aria-label="Dropdown menu for keyword Biomarkers"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link"
|
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href="/?term=%22Biomarkers%22%5Bnm%5D&sort=date&sort_order=desc"
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data-href="/?term=%22Biomarkers%22%5Bnm%5D&sort=date&sort_order=desc"
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ref="linksrc=search_in_pubmed_keyword_link&keyword="Biomarkers"[nm]"
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data-ga-category="search"
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data-ga-action="substance"
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data-ga-label="Biomarkers">
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Search in PubMed
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</a></li><li><a class="search-in-mesh-link dropdown-block-link"
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href="https://www.ncbi.nlm.nih.gov/mesh?term=%22Biomarkers%22"
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Search in MeSH
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</a></li><li><a class="add-to-search-link dropdown-block-link"
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data-search-term=""Biomarkers"[nm]"
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data-ga-category="search"
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data-ga-action="add_to_search"
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data-ga-label=""Biomarkers"[nm]"
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href="#">
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Add to Search
|
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</a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link"
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aria-label="Toggle dropdown menu for keyword Presenilin-1"
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tabindex="0"
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aria-controls="keyword-actions-substances-3"
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aria-expanded="false"
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data-pinger-ignore>
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Presenilin-1
|
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</button><div id="keyword-actions-substances-3"
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class="keyword-actions-dropdown dropdown dropdown-container"
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hidden
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aria-label="Dropdown menu for keyword Presenilin-1"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link"
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href="/?term=%22Presenilin-1%22%5Bnm%5D&sort=date&sort_order=desc"
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data-href="/?term=%22Presenilin-1%22%5Bnm%5D&sort=date&sort_order=desc"
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ref="linksrc=search_in_pubmed_keyword_link&keyword="Presenilin-1"[nm]"
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data-ga-category="search"
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data-ga-action="substance"
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data-ga-label="Presenilin-1">
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Search in PubMed
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</a></li><li><a class="search-in-mesh-link dropdown-block-link"
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ref="linksrc=search_in_mesh_link"
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href="https://www.ncbi.nlm.nih.gov/mesh?term=%22Presenilin-1%22"
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Search in MeSH
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</a></li><li><a class="add-to-search-link dropdown-block-link"
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