Apolipoprotein E ϵ4 and Incidence of Alzheimer Disease in a Community Population of Older Persons

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 ϵ4 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/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 ϵ3/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.