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 ε 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 ε4 allele was less than that found in most family and case-control studies. Persons with the ε4 or ε3/ε4 genotypes had 2.27 (95% confidence interval, 1.06-4.89) times the risk of incident disease compared with those with the ε/ε3 genotype. The ε4 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 ε4 allele on risk of AD did not appear to vary with age. Conclusions.-The apolipoprotein E ε4 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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