Apolipoprotein E: Risk factor for Alzheimer disease

The apolipoprotein E gene (APOE) has three common alleles (ε2, ε3, and ε4) that determine six genotypes in the general population. In this study, we examined 77 patients with late-onset Alzheimer disease (AD), along with an equal number of age- and sex-matched controls, for an association with the APOE-ε4 allele. We show that the frequency of this allele among AD patients was significantly higher than that among the control population (.351 vs. .130, P = .000006). The genotype frequencies also differed between the two groups (P = .0002), with the APOE-ε4/ε3 genotype being the most common in the AD group and the APOE-ε3/ε3 being the most common in the control group. In the AD group, homozygosity for ε4 was found in nine individuals, whereas none was found in the control group. The odds ratio for AD, when associated with one or two ε4 alleles, was 4.6 (95% confidence interval [CI] 1.9- 12.3), while the odds ratio for AD, when associated with heterozygosity for APOE-ε4, was 3.6 (95% CI 1.5-9.8). Finally, the median age at onset among the AD patients decreased from 83 to 78 to 74 years as the number of APOE- ε4 alleles increased from 0 to 1 to 2, respectively (test for trend, P = .001). Our data, which are in agreement with recent reports, suggest that the APOE-ε4 allele is associated with AD and that this allelic variant may be an important risk factor for susceptibility to AD in the general population.