Apolipoprotein E epsilon4 and incidence of Alzheimer disease in a community population of older persons.

Abstract

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. Community-based cohort study. East Boston, Mass. A random sample of 578 community residents aged 65 years and older free of AD. Clinical diagnosis of AD by uniform, structured evaluation. 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. 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.