The distribution of apolipoprotein E (APOE) genotypes as a function of age and sex has been examined in a French population of 417 Alzheimer disease (AD) patients and 1,030 control subjects. When compared to the APOE epsilon3 allele, an increased risk associated with the APOE epsilon4 allele (odds ratio [OR] [epsilon4] = 2.7 with 95% confidence interval [CI] = 2.0-3.6; P < .001) and a protective effect of the APOE epsilon2 allele (OR[epsilon2] = 0.5 with 95% CI = 0.3-0.98; P = .012) were retrieved. An effect of the epsilon4 allele dosage on susceptibility was confirmed (OR[epsilon4/epsilon4] vs. the epsilon3/epsilon3 genotype = 11.2 [95% CI = 4.0-31.6]; OR[epsilon3/epsilon4] vs. the epsilon3/epsilon3 genotype = 2.2 [95% CI = 1.5-3.5]). The frequency of the epsilon4 allele was lower in male cases than in female cases, but, since a similar difference was found in controls, this does not lead to a difference in OR between sex. ORs for the epsilon4 allele versus the epsilon3 allele, OR(epsilon4), were not equal in all age classes: OR(epsilon4) in the extreme groups with onset at < 60 years or > 79 years were significantly lower than those from the age groups 60-79 years. In epsilon3/epsilon4 individuals, sex-specific lifetime risk estimates by age 85 years (i.e., sex-specific penetrances by age 85 years) were 0.14 (95% CI 0.04-0.30) for men and 0.17 (95% CI 0.09-0.28) for women.