Apolipoprotein E, survival in Alzheimer's disease patients, and the competing risks of death and Alzheimer's disease
Abstract
The apolipoprotein E (APOE) epsilon 4 allele carries an increased risk of a patient developing Alzheimer's disease (AD) while the epsilon 2 allele carries a decreased risk. We compared survival from the onset of AD in subjects with different numbers of epsilon 4 alleles and evaluated changes in genotypic frequencies with age. Two subject groups were investigated: unrelated AD case and control subjects, and affected and unaffected members from 74 multiplex AD families. In both subject groups, survival from onset decreased with increasing onset age, was longer in women, and was unrelated to epsilon 4 gene dose. The epsilon 2/epsilon 3 genotype became more common with age (p = 0.004). The epsilon 4 allele decreased in frequency with age in all patient groups but, unexpectedly, remained unchanged in control subjects. We conclude that the progression of AD is not strongly related to epsilon 4 gene dose, that the higher prevalence of AD in women may involve the longer survival of affected women, and that AD and death are competing risks involving APOE that change over time.
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Carriers of the APOE ε4 allele have greatly increased Alzheimer's disease risk and enhanced brain Aβ deposition.
“Carriers of the apolipoprotein E (APOE) ε4 allele demonstrate greatly increased AD risk and enhanced brain Aβ deposition.”
From Blocking the apoE/Aβ interaction ameliorates Aβ-related pathology in APOE ε2 and ε4 targeted replacement Alzheimer model mice (2014) · cites this paper as [6]
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- Authors
- Corder, E. H., Saunders, A. M., Strittmatter, W. J., Schmechel, D. E., Gaskell, P. C., Rimmler, J. B., Locke, P. A., Conneally, P. M., Schmader, K. E., Tanzi, R. E., Gusella, J. F., Small, G. W., Roses, A. D., Pericak-Vance, M. A., & Haines, J. L.
- Affiliations
- Duke Medical Center (US)
- From the Divisions of Neurology (Drs. Corder, Saunders, Strittmatter, Schmechel, Roses, and Pericak-Vance, and P.C. Gaskell and J.B. Rimmler) and Neurobiology (Drs. Strittmatter, Schmechel, and Roses), Joseph and Kathleen Bryan Alzheimer's Disease Research Center, Duke University Medical Center, Durham, NC; the GRECC Durham VA Medical Center (Drs. Schmechel and Schmader), Durham, NC; the Center for the Study of Aging and Human Development (Dr. Schmader), Duke University Medical Center, Durham, NC;...
- Venue
- Neurology
- Published
- 1995-07
- Volume
- 45
- Issue
- 7
- Pages
- 1323-1328
- ISSN
- 0028-3878 (ISSN-L)
- 1526-632X
- OpenAlex
- W2156765601
- Cited by
- 169
- References
- 0
- Citations by year
- 2026: 3 · 2025: 4 · 2024: 1 · 2022: 1 · 2021: 3 · 2020: 2 · 2019: 2 · 2018: 2 · 2017: 1 · 2016: 4 · 2015: 5 · 2014: 5 · 2013: 4 · 2012: 1
- FWCI
- 12.12
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neurology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute on Aging (AG05 128, P50AG005128, U24AG021886)
- National Institute of Neurological Disorders and Stroke (P01NS026630, NS531153, NS 26630)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Keywords
- apolipoprotein E, APOE ε4, Alzheimer's disease, gene dosage, sex differences, multiplex families
- MeSH terms
- Aged, Alleles, Alzheimer Disease, Apolipoproteins E, Female, Genotype, Humans, Male, Middle Aged, Risk Factors, Age of Onset, Apolipoprotein E3, Apolipoprotein E4
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