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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 allele may promote AD at multiple steps of AD pathology: - APOE3 & APOE4 were tied to 71.5% to 92.7% of AD cases across 4 cohorts, - apo E binds to A4/42 & APOE3 & APOE4 increase the tendency for A4/42 to precipitate relative to APOE2 [2] - apo E4 allegedly has least anti-oxidant potential of apo E alleles [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 - APOE3 & APOE4 were tied to 71.5% to 92.7% of cases across 4 cohorts* , * APOE3 is considered the wild type allele & its frequency relative to that of APOE4 may help explain this finding

Interactions

disease interactions

General

familial Alzheimer's disease (FAD)

Database Correlations

OMIM correlations MORBIDMAP 107741 Entrez Gene 99

References

  1. Lendon & Craddock, Trends in the Neurosciences 24:557, 2001
  2. Yamaguchi et al, J. Neuropathol Exp Neurol 60:731, 2001
  3. Lauderback et al, Brain Res 924:90, 2002
  4. Geriatric Review Syllabus, 11th edition (GRS11) Harper GM, Lyons WL, Potter JF (eds) American Geriatrics Society, 2022
  5. 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
  6. 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
  7. 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
  8. George J Alzheimer's Risk May Be Driven by a Single Gene. APOE's contribution to disease burden has been "long underestimated," researcher says. MedPage Today. January 9, 2026 https://www.medpagetoday.com/neurology/alzheimersdisease/119357 - Williams DM, Heikkinen S, Hiltunen M et al The proportion of Alzheimer's disease attributable to apolipoprotein E. npj Dementia, 2026. 2,1 Jan 9 Not yet indexed in PubMed https://www.nature.com/articles/s44400-025-00045-9