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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

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
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
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
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
Genetic aspects of Alzheimer disease.
Bird TD
Genet Med 2008 Apr;10(4):231-9. doi: 10.1097/GIM.0b013e31816b64dc. PMID: 18414205Free PMC Article

Diagnosis

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
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
Intramembrane proteolysis by gamma-secretase.
Steiner H, Fluhrer R, Haass C
J Biol Chem 2008 Oct 31;283(44):29627-31. Epub 2008 Jul 23 doi: 10.1074/jbc.R800010200. PMID: 18650432Free PMC Article
Genetic aspects of Alzheimer disease.
Bird TD
Genet Med 2008 Apr;10(4):231-9. doi: 10.1097/GIM.0b013e31816b64dc. PMID: 18414205Free PMC Article

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

Retinal Imaging Findings in Carriers With PSEN1-Associated Early-Onset Familial Alzheimer Disease Before Onset of Cognitive Symptoms.
Armstrong GW, Kim LA, Vingopoulos F, Park JY, Garg I, Kasetty M, Silverman RF, Zeng R, Douglas VP, Lopera F, Baena A, Giraldo M, Norton D, Cronin-Golomb A, Arboleda-Velasquez JF, Quiroz YT, Miller JB
JAMA Ophthalmol 2021 Jan 1;139(1):49-56. doi: 10.1001/jamaophthalmol.2020.4909. PMID: 33180114Free PMC Article
Evolutionary History of Alzheimer Disease-Causing Protein Family Presenilins with Pathological Implications.
Khan AA, Ali RH, Mirza B
J Mol Evol 2020 Nov;88(8-9):674-688. Epub 2020 Oct 1 doi: 10.1007/s00239-020-09966-w. PMID: 33001284
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
Presymptomatic cortical thinning in familial Alzheimer disease: A longitudinal MRI study.
Weston PS, Nicholas JM, Lehmann M, Ryan NS, Liang Y, Macpherson K, Modat M, Rossor MN, Schott JM, Ourselin S, Fox NC
Neurology 2016 Nov 8;87(19):2050-2057. Epub 2016 Oct 12 doi: 10.1212/WNL.0000000000003322. PMID: 27733562Free 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

Clinical prediction guides

Differential effects of familial Alzheimer's disease-causing mutations on amyloid precursor protein (APP) trafficking, proteolytic conversion, and synaptogenic activity.
Schilling S, Pradhan A, Heesch A, Helbig A, Blennow K, Koch C, Bertgen L, Koo EH, Brinkmalm G, Zetterberg H, Kins S, Eggert S
Acta Neuropathol Commun 2023 Jun 1;11(1):87. doi: 10.1186/s40478-023-01577-y. PMID: 37259128Free 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
Converging roles of PSENEN/PEN2 and CLN3 in the autophagy-lysosome system.
Klein M, Kaleem A, Oetjen S, Wünkhaus D, Binkle L, Schilling S, Gjorgjieva M, Scholz R, Gruber-Schoffnegger D, Storch S, Kins S, Drewes G, Hoffmeister-Ullerich S, Kuhl D, Hermey G
Autophagy 2022 Sep;18(9):2068-2085. Epub 2021 Dec 29 doi: 10.1080/15548627.2021.2016232. PMID: 34964690Free 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
Interleukin-1 and the immunogenetics of Alzheimer disease.
Mrak RE, Griffin WS
J Neuropathol Exp Neurol 2000 Jun;59(6):471-6. doi: 10.1093/jnen/59.6.471. PMID: 10850859Free PMC Article

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