Apolipoprotein E ε4 Allele and the Lifetime Risk of Alzheimer's Disease: What Physicians Know, and What They Should Know
Abstract
Background Published studies now show a clear association between Alzheimer's disease (AD) and the apolipoprotein E epsilon 4 allele (APOE* epsilon 4). The clinical value of this information to estimate a healthy individual's lifetime risk of AD has not been well delineated. Physicians dealing with AD may not know either the lifetime risk of developing AD or the effect of the APOE genotype on this risk. Because the lifetime risk of AD depends in part on life expectancy, and available figures on APOE are not population based, a computation is necessary to derive risk estimates useful to physicians. Objectives To estimate the lifetime risk of AD and the effect of APOE genotype information on that risk and to assess the knowledge of these risks among physicians who manage patients with dementia. Design Estimation of risk of AD and survey of physician awareness. The lifetime risk of developing AD without APOE genotype information was first computed for 65-year-olds from existing epidemiologic studies of age-related AD incidence and an actuarial life-table analysis. Using this computed a priori risk of AD and published studies of APOE genotypes in individuals with and without AD, we used a Bayesian analysis to determine the risk of developing AD, with and without an APOE* epsilon 4 allele, for unaffected 65-year-olds. To assess physician knowledge of the lifetime risk of AD and the effect of APOE genotyping on the risk, 50 neurologists, internists, geriatricians, geriatric psychia…
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The APOE polymorphism is the most studied, successfully replicated, and well-established risk factor for Alzheimer's disease, with APOE*2 protective and APOE*4 risk compared to APOE*3.
“The APOE polymorphism is the most studied, successfully replicated, and well-established risk factor for AD where APOE*2 is the protective allele and APOE*4 is the risk allele as compared to APOE*3 [7–10].”
From Genome-wide analysis identifies novel loci influencing plasma apolipoprotein E concentration and Alzheimer’s disease risk (2023) · cites this paper as [7]
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- Authors
- Seshadri, S.
- Affiliations
- University of Massachusetts Chan Medical School (US)
- Corresponding author
- Seshadri, Sudha
- ORCID
- Seshadri, Sudha
- Venue
- Archives of Neurology
- Publisher
- American Medical Association (AMA)
- Published
- 1995-11-01
- Volume
- 52
- Issue
- 11
- Pages
- 1074
- ISSN
- 0003-9942 (ISSN-L)
- OpenAlex
- W1996807233
- Cited by
- 163
- References
- 6
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 3 · 2023: 2 · 2022: 5 · 2021: 3 · 2020: 6 · 2019: 2 · 2018: 1 · 2017: 5 · 2016: 4 · 2015: 2 · 2014: 4 · 2013: 3 · 2012: 7
- FWCI
- 9.13
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Archives of Neurology (publishedVersion)
- PubMed (publishedVersion)
- The Journal of the American Medical Association (JAMA) Network (American Medical Association) (submittedVersion)
- Funders
- U.S. Public Health Service (2-P50A605134-11)
- National Institute of Neurological Disorders and Stroke (R01NS017950)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
- Keywords
- Alzheimer's disease, APOE ε4, lifetime risk, genetic risk prediction, physician knowledge, dementia management, genetic testing, risk communication, age-related incidence, family history of Alzheimer's disease, neurologists, geriatricians, general practitioners, internists, life expectancy
- MeSH terms
- Actuarial Analysis, Adult, Aged, Alleles, Alzheimer Disease, Apolipoproteins E, Bayes Theorem, Humans, Risk Factors, Apolipoprotein E4
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