THE APOLIPOPROTEIN EPSILON-4 ALLELE IN PATIENTS WITH ALZHEIMERS-DISEASE

Apolipoprotein E (APO-E) binds to the beta-amyloid peptide and is present in senile neuritic plaques in Alzheimer's disease (AD). The epsilon4 isoform of APO-E has been associated with both sporadic and familial late-onset AD, implying a causal role. Among patients and control subjects similar in age, gender, and ethnic group from the New York City community of Washington Heights-Inwood, we found that the odds ratio (OR) for AD associated with homozygosity for APO-epsilon4 was 17.9 (95% confidence interval [CI], 4.6-69.8) and that associated with heterozygosity for APO-epsilon4 was 4.2 (95% CI, 1.8-9.5), compared with persons with other APO-E genotypes. The association was stronger among patients with sporadic disease (OR = 10.3; 95% Cl, 3.4-31.1) than among those with a family history of dementia in a first-degree relative (OR = 0.9; 95% CI, 0.1-13.5). The association between APO-epsilon4 and AD did not differ according to age at onset (<65 vs greater-than-or-equal-to 65), but appeared to vary across the 3 ethnic groups investigated (black, Hispanic, and white). Our data confirm the association between AD and APO-epsilon4 and support the hypothesis that the APO-epsilon4 allele either confers genetic susceptibility to AD or may be in linkage disequilibrium with another susceptibility locus. Ethnic variability in the allelic frequency of APO-epsilon4 in the elderly warrants further investigation.