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familial Alzheimer's disease type 2 (FAD2), apo E4 associated
Epidemiology:
- FAD2 accounts for 50% of AD cases. [1]
Pathology:
- Apo E & the E4 allele may promote AD at multiple steps of AD pathology:
a) apo E binds to A4/42 & apo E4 increases the tendency for A4/42 to precipitate relative to other apo E alleles [2]
b) apo E4 allegedly has least anti-oxidant potential of apo Ealleles [2]
Clinical significance:
- the apolipoprotein E (apo E) gene a susceptibility & disease- modifying factor for Alzheimer's disease (AD) with the apo E4 allele conferring the greatest risk of AD
- each apo-E4 allele confers a 3-4-fold increased risk of AD [4,5,6,7]
- thus not everyone bearing an apo E4 allele (or 2 apo E4 alleles) will develop AD
- conversely not everyone with AD has an apo E4 allele
Interactions
disease interactions
General
familial Alzheimer's disease (FAD)
Database Correlations
OMIM correlations
MORBIDMAP 107741
Entrez Gene 99
References
- Lendon & Craddock, Trends in the Neurosciences 24:557, 2001
- Yamaguchi et al, J. Neuropathol Exp Neurol 60:731, 2001
- Lauderback et al, Brain Res 924:90, 2002
- Geriatric Review Syllabus, 11th edition (GRS11)
Harper GM, Lyons WL, Potter JF (eds)
American Geriatrics Society, 2022
- Lane-Donovan C, Herz J.
ApoE, ApoE Receptors, and the synapse in Alzheimer's disease.
Trends Endocrinol Metab. 2017;28(4):273-284
PMID: 28057414 PMCID: PMC5366078Free PMC article
https://www.cell.com/trends/endocrinology-metabolism/fulltext/S1043-2760(16)30170-9
- Uddin MS, Kabir MT, Al Mamun A et al.
APOE and Alzheimer's disease: evidence mounts that targeting APOE4 may combat
Alzheimer's pathogenesis.
Mol Neurobiol. 2019;56(4):2450-2465
PMID: 30032423
https://link.springer.com/article/10.1007/s12035-018-1237-z
- Zhao N, Liu CC, Qiao W, et al.
Apolipoprotein E, receptors, and modulation of Alzheimer's disease.
Biol Psychiatry. 2018;83(4):347-357
PMID: 28434655 PMCID: PMC5599322Free PMC article
https://www.biologicalpsychiatryjournal.com/article/S0006-3223(17)31358-6/fulltext