Apolipoprotein E element 4 association with dementia in a population-based study: The Framingham Study

Myers, R. H.; Schaefer, E. J.; Wilson, P.W.F.; D'Agostino, R.; Ordovas, J. M.; Espino, A.; Au, R.; White, R. F.; Knoefel, J. E.; Cobb, J. L.; McNulty, K. A.; Beiser, A.; Wolf, P. A.

doi:10.1212/wnl.46.3.673

Cited by 346Dementia and Cognitive Impairment ResearchAlzheimer's disease research and treatmentsLipoproteins and Cardiovascular Health

Apolipoprotein E element 4 association with dementia in a population-based study: The Framingham Study

Myers, R. H., Schaefer, E. J., Wilson, P.W.F., D'Agostino, R., Ordovas, J. M., Espino, A., Au, R., White, R. F. +5 more·1996·Neurology

DOI 10.1212/wnl.46.3.673

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Abstract

Apolipoprotein E type 4 allele (apoE epsilon4) is associated with Alzheimer's disease (AD) in the late-onset familial form and in sporadic cases, but the age-associated risk in a randomly sampled elderly population is not established. We examined the association of apoE epsilon4 with AD and other dementias (mainly multi-infarct or dementia following stroke) in 1,030 persons aged 71 to 100 years in the population-based Framingham Study cohort. Kaplan-Meier survival analysis revealed that 55% of the apoE epsilon4/epsilon4 homozygotes developed AD by age 80, whereas 27% of apoE epsilon3/epsilon4 heterozygotes developed AD by age 85, and 9% of those without a 4 allele developed AD by age 85 years. In comparison with persons without a 4 allele, the risk ration for AD was 3.7 (95% CI = 1.9 to 7.5) for apoE epsilon3/epsilon4 heterozygotes and 30.1 (95% CI = 10.7 to 84.4) for apoE epsilon4 homozygotes. ApoE epsilon2 (2/2, 2/3, or 2/4 genotypes) was associated with an absence of AD. One-half (n=21) of the 43 AD patients were either homozygous or heterozygous for apoE epsilon4. We found evidence for an association of apoE epsilon4 with other dementia, primarily multi-infarct dementia and stroke. The risk ratio was 2.3 (95% CI = 0.9 to 6.1) for non-AD dementias among persons with apoE epsilon3/epsilon4. Although the apoE epsilon4 allele is a potent risk factor for AD and may be associated with other forms of dementia, most apoE epsilon4 carriers do not develop dementia, and about one-ha…

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Being homozygous or heterozygous for the ε4 allele increases the risk of LOAD 4-fold and lowers the age of onset of the disease.
“Being homozygous or heterozygous for the ⑀4 allele increases the risk of LOAD 4-fold and lowers the age of onset of the disease (4,5).”
From Molecular Basis for Increased Risk for Late-onset Alzheimer Disease Due to the Naturally Occurring L28P Mutation in Apolipoprotein E4 (2014) · cites this paper as [5]

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Authors: Myers, R. H., Schaefer, E. J., Wilson, P. W. F., D'Agostino, R., Ordovas, J. M., Espino, A., Au, R., White, R. F., Knoefel, J. E., Cobb, J. L., McNulty, K. A., Beiser, A., & Wolf, P. A.
Affiliations: Boston University (US)
ORCID: Myers, R. H.
Schaefer, E. J.
Wilson, P.W.F.
Au, R.
White, R. F.
Knoefel, J. E.
Beiser, A.
Wolf, P. A.
Venue: Neurology
Publisher: Ovid Technologies (Wolters Kluwer Health)
Published: 1996-03
Volume: 46
Issue: 3
Pages: 673-677
ISSN: 0028-3878 (ISSN-L)
1526-632X
DOI: 10.1212/wnl.46.3.673
OpenAlex: W1972509050
Cited by: 346
References: 30
Citations by year: 2026: 2 · 2025: 6 · 2024: 1 · 2023: 4 · 2022: 10 · 2021: 12 · 2020: 5 · 2019: 10 · 2018: 8 · 2017: 6 · 2016: 6 · 2015: 13 · 2014: 11 · 2013: 16 · 2012: 24
FWCI: 16.71
Type: journal article
Language: en
Open access: closed
Locations: Neurology (publishedVersion)
PubMed (publishedVersion)
Funders: National Institutes of Health (n01hc038038-022)
National Institute on Aging (2-R01-AG08122-06, R01AG008122)
National Heart, Lung, and Blood Institute (N01-HC-38038)
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: APOE ε4, Alzheimer's disease, dementia, multi-infarct dementia, stroke, genetic risk factors, APOE genotype, Framingham Heart Study, older adults, positive predictive value, genetic screening
MeSH terms: Adult, Aged, Aged, 80 and over, Alleles, Alzheimer Disease, Apolipoproteins E, Base Sequence, Dementia, Female, Humans, Longitudinal Studies, Male, Middle Aged, Molecular Sequence Data, Sensitivity and Specificity, Cohort Studies, Molecular Probes, Incidence, Odds Ratio, Apolipoprotein E4

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Apolipoprotein E element 4 association with dementia in a population-based study: The Framingham Study

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