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Familial Alzheimer disease(FAD)

MedGen UID:
82914
•Concept ID:
C0276496
•
Disease or Syndrome
Synonym: FAD
 
Monarch Initiative: MONDO:0100087

Definition

A degenerative disease of the brain that causes gradual loss of memory, judgment, and the ability to function socially. About 25% of all Alzheimer disease is familial (more than 2 people in a family have AD). When Alzheimer disease begins before 60 or 65 years of age (early-onset AD) about 60% of the cases are familial (also known as Early-onset familial AD). These cases appear to be inherited in an autosomal dominant manner. [from MONDO]

Professional guidelines

PubMed

Plasma signaling proteins in persons at genetic risk for Alzheimer disease: influence of APOE genotype.
Ringman JM, Elashoff D, Geschwind DH, Welsh BT, Gylys KH, Lee C, Cummings JL, Cole GM
Arch Neurol 2012 Jun;69(6):757-64. doi: 10.1001/archneurol.2012.277. PMID: 22689192Free PMC Article
Genetic counseling for early-onset familial Alzheimer disease in large Aboriginal kindred from a remote community in British Columbia: unique challenges and possible solutions.
Butler R, Dwosh E, Beattie BL, Guimond C, Lombera S, Brief E, Illes J, Sadovnick AD
J Genet Couns 2011 Apr;20(2):136-42. Epub 2010 Oct 7 doi: 10.1007/s10897-010-9334-9. PMID: 20927575
Apolipoprotein E4 allele as a predictor of cholinergic deficits and treatment outcome in Alzheimer disease.
Poirier J, Delisle MC, Quirion R, Aubert I, Farlow M, Lahiri D, Hui S, Bertrand P, Nalbantoglu J, Gilfix BM, Gauthier S
Proc Natl Acad Sci U S A 1995 Dec 19;92(26):12260-4. doi: 10.1073/pnas.92.26.12260. PMID: 8618881Free PMC Article

Recent clinical studies

Etiology

Cerebral Small Vessel Disease in Sporadic and Familial Alzheimer Disease.
Kalaria RN, Sepulveda-Falla D
Am J Pathol 2021 Nov;191(11):1888-1905. Epub 2021 Jul 28 doi: 10.1016/j.ajpath.2021.07.004. PMID: 34331941Free PMC Article
A rare loss-of-function variant of ADAM17 is associated with late-onset familial Alzheimer disease.
Hartl D, May P, Gu W, Mayhaus M, Pichler S, Spaniol C, Glaab E, Bobbili DR, Antony P, Koegelsberger S, Kurz A, Grimmer T, Morgan K, Vardarajan BN, Reitz C, Hardy J, Bras J, Guerreiro R, Balling R, Schneider JG, Riemenschneider M; AESG
Mol Psychiatry 2020 Mar;25(3):629-639. Epub 2018 Jul 9 doi: 10.1038/s41380-018-0091-8. PMID: 29988083Free PMC Article
TREM2 variants: new keys to decipher Alzheimer disease pathogenesis.
Colonna M, Wang Y
Nat Rev Neurosci 2016 Apr;17(4):201-7. Epub 2016 Feb 25 doi: 10.1038/nrn.2016.7. PMID: 26911435
Familial Alzheimer disease: decreases in CSF Abeta42 levels precede cognitive decline.
Moonis M, Swearer JM, Dayaw MP, St George-Hyslop P, Rogaeva E, Kawarai T, Pollen DA
Neurology 2005 Jul 26;65(2):323-5. doi: 10.1212/01.wnl.0000171397.32851.bc. PMID: 16043812
Variable expression of familial Alzheimer disease associated with presenilin 2 mutation M239I.
Finckh U, Alberici A, Antoniazzi M, Benussi L, Fedi V, Giannini C, Gal A, Nitsch RM, Binetti G
Neurology 2000 May 23;54(10):2006-8. doi: 10.1212/wnl.54.10.2006. PMID: 10822446

Diagnosis

TRIM22 facilitates autophagosome-lysosome fusion by mediating the association of GABARAPs and PLEKHM1.
Heo H, Park H, Lee MS, Kim J, Kim J, Jung SY, Kim SK, Lee S, Chang J
Autophagy 2024 May;20(5):1098-1113. Epub 2023 Dec 7 doi: 10.1080/15548627.2023.2287925. PMID: 38009729Free PMC Article
Polygenic risk score penetrance & recurrence risk in familial Alzheimer disease.
Qiao M, Lee AJ, Reyes-Dumeyer D, Tosto G, Faber K, Goate A, Renton A, Chao M, Boeve B, Cruchaga C, Pericak-Vance M, Haines JL, Rosenberg R, Tsuang D, Sweet RA, Bennett DA, Wilson RS, Foroud T, Mayeux R, Vardarajan BN
Ann Clin Transl Neurol 2023 May;10(5):744-756. Epub 2023 Mar 22 doi: 10.1002/acn3.51757. PMID: 36946865Free PMC Article
Polygenic risk scores in familial Alzheimer disease.
Tosto G, Bird TD, Tsuang D, Bennett DA, Boeve BF, Cruchaga C, Faber K, Foroud TM, Farlow M, Goate AM, Bertlesen S, Graff-Radford NR, Medrano M, Lantigua R, Manly J, Ottman R, Rosenberg R, Schaid DJ, Schupf N, Stern Y, Sweet RA, Mayeux R
Neurology 2017 Mar 21;88(12):1180-1186. Epub 2017 Feb 17 doi: 10.1212/WNL.0000000000003734. PMID: 28213371Free PMC Article
Familial Alzheimer disease: decreases in CSF Abeta42 levels precede cognitive decline.
Moonis M, Swearer JM, Dayaw MP, St George-Hyslop P, Rogaeva E, Kawarai T, Pollen DA
Neurology 2005 Jul 26;65(2):323-5. doi: 10.1212/01.wnl.0000171397.32851.bc. PMID: 16043812
Variable expression of familial Alzheimer disease associated with presenilin 2 mutation M239I.
Finckh U, Alberici A, Antoniazzi M, Benussi L, Fedi V, Giannini C, Gal A, Nitsch RM, Binetti G
Neurology 2000 May 23;54(10):2006-8. doi: 10.1212/wnl.54.10.2006. PMID: 10822446

Therapy

Multi-Target Effects of the Cannabinoid CP55940 on Familial Alzheimer's Disease PSEN1 E280A Cholinergic-Like Neurons: Role of CB1 Receptor.
Soto-Mercado V, Mendivil-Perez M, Jimenez-Del-Rio M, Velez-Pardo C
J Alzheimers Dis 2021;82(s1):S359-S378. doi: 10.3233/JAD-201045. PMID: 33252082Free PMC Article
Anti-Alzheimer Therapeutic Drugs Targeting γ-Secretase.
Tan Y, Zhang Q, Wong SG, Hua Q
Curr Top Med Chem 2016;16(5):549-57. doi: 10.2174/1568026615666150813144151. PMID: 26268329
A conceptual framework and ethics analysis for prevention trials of Alzheimer Disease.
Peters KR, Lynn Beattie B, Feldman HH, Illes J
Prog Neurobiol 2013 Nov;110:114-23. Epub 2013 Jan 21 doi: 10.1016/j.pneurobio.2012.12.001. PMID: 23348495
Familial Alzheimer disease in Latinos: interaction between APOE, stroke, and estrogen replacement.
Rippon GA, Tang MX, Lee JH, Lantigua R, Medrano M, Mayeux R
Neurology 2006 Jan 10;66(1):35-40. doi: 10.1212/01.wnl.0000191300.38571.3e. PMID: 16401842Free PMC Article
Apolipoprotein E: high-avidity binding to beta-amyloid and increased frequency of type 4 allele in late-onset familial Alzheimer disease.
Strittmatter WJ, Saunders AM, Schmechel D, Pericak-Vance M, Enghild J, Salvesen GS, Roses AD
Proc Natl Acad Sci U S A 1993 Mar 1;90(5):1977-81. doi: 10.1073/pnas.90.5.1977. PMID: 8446617Free PMC Article

Prognosis

Polygenic risk scores in familial Alzheimer disease.
Tosto G, Bird TD, Tsuang D, Bennett DA, Boeve BF, Cruchaga C, Faber K, Foroud TM, Farlow M, Goate AM, Bertlesen S, Graff-Radford NR, Medrano M, Lantigua R, Manly J, Ottman R, Rosenberg R, Schaid DJ, Schupf N, Stern Y, Sweet RA, Mayeux R
Neurology 2017 Mar 21;88(12):1180-1186. Epub 2017 Feb 17 doi: 10.1212/WNL.0000000000003734. PMID: 28213371Free PMC Article
Insights into Alzheimer disease pathogenesis from studies in transgenic animal models.
Schaeffer EL, Figueiro M, Gattaz WF
Clinics (Sao Paulo) 2011;66 Suppl 1(Suppl 1):45-54. doi: 10.1590/s1807-59322011001300006. PMID: 21779722Free PMC Article
Familial Alzheimer disease: decreases in CSF Abeta42 levels precede cognitive decline.
Moonis M, Swearer JM, Dayaw MP, St George-Hyslop P, Rogaeva E, Kawarai T, Pollen DA
Neurology 2005 Jul 26;65(2):323-5. doi: 10.1212/01.wnl.0000171397.32851.bc. PMID: 16043812
Detection of the presenilin 1 gene mutation (M139T) in early-onset familial Alzheimer disease in Spain.
Queralt R, Ezquerra M, Castellví M, Lleó A, Blesa R, Oliva R
Neurosci Lett 2001 Feb 23;299(3):239-41. doi: 10.1016/s0304-3940(01)01498-7. PMID: 11165779
Variable expression of familial Alzheimer disease associated with presenilin 2 mutation M239I.
Finckh U, Alberici A, Antoniazzi M, Benussi L, Fedi V, Giannini C, Gal A, Nitsch RM, Binetti G
Neurology 2000 May 23;54(10):2006-8. doi: 10.1212/wnl.54.10.2006. PMID: 10822446

Clinical prediction guides

Cell signaling abnormalities may drive neurodegeneration in familial Alzheimer disease.
Robakis NK
Neurochem Res 2014;39(3):570-5. Epub 2013 Feb 23 doi: 10.1007/s11064-013-1003-6. PMID: 23436150Free PMC Article
Familial Alzheimer disease: decreases in CSF Abeta42 levels precede cognitive decline.
Moonis M, Swearer JM, Dayaw MP, St George-Hyslop P, Rogaeva E, Kawarai T, Pollen DA
Neurology 2005 Jul 26;65(2):323-5. doi: 10.1212/01.wnl.0000171397.32851.bc. PMID: 16043812
Variable expression of familial Alzheimer disease associated with presenilin 2 mutation M239I.
Finckh U, Alberici A, Antoniazzi M, Benussi L, Fedi V, Giannini C, Gal A, Nitsch RM, Binetti G
Neurology 2000 May 23;54(10):2006-8. doi: 10.1212/wnl.54.10.2006. PMID: 10822446
Evidence for phosphorylation and oligomeric assembly of presenilin 1.
Seeger M, Nordstedt C, Petanceska S, Kovacs DM, Gouras GK, Hahne S, Fraser P, Levesque L, Czernik AJ, George-Hyslop PS, Sisodia SS, Thinakaran G, Tanzi RE, Greengard P, Gandy S
Proc Natl Acad Sci U S A 1997 May 13;94(10):5090-4. doi: 10.1073/pnas.94.10.5090. PMID: 9144195Free PMC Article
The AD1 locus in familial Alzheimer disease.
Lawrence S, Keats BJ, Morton NE
Ann Hum Genet 1992 Oct;56(4):295-301. doi: 10.1111/j.1469-1809.1992.tb01156.x. PMID: 1492744

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