Apolipoprotein E epsilon4 and incidence of Alzheimer disease in a community population of older persons.
Meyers Primary Care Institute
Medical Subject Headings
Aged; Alleles; Alzheimer Disease; Apolipoproteins E; Cohort Studies; Female; Gene Frequency; Genotype; Humans; Incidence; Logistic Models; Male; Multivariate Analysis; Risk Factors
Health Services Research | Medicine and Health Sciences
OBJECTIVE: To examine the relation between apolipoprotein E status and risk of Alzheimer disease (AD) in a defined population and estimate the fraction of incident AD attributable to the epsilon4 allele. DESIGN: Community-based cohort study. SETTING: East Boston, Mass. PARTICIPANTS: A random sample of 578 community residents aged 65 years and older free of AD. MAIN OUTCOME MEASURE: Clinical diagnosis of AD by uniform, structured evaluation. RESULTS: The increased risk of AD associated with the presence of the epsilon4 allele was less than that found in most family and case-control studies. Persons with the epsilon4/epsilon4 or epsilon3/epsilon4 genotypes had 2.27 (95% confidence interval, 1.06-4.89) times the risk of incident disease compared with those with the epsilon3/epsilon3 genotype. The epsilon4 allele accounted for a fairly small fraction of the incidence of AD; if the allele did not exist or had no effect on disease risk, the incidence would be reduced by only 13.7%. The effect of the epsilon4 allele on risk of AD did not appear to vary with age. CONCLUSIONS: The apolipoprotein E epsilon4 allele is an important genetic risk factor for AD but accounts for a fairly small fraction of disease occurrence in this population-based study. Continued efforts to identify other environmental and genetic risk factors are warranted.
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Citation: JAMA. 1997 Mar 12;277(10):822-4.