ALZHEIMERS-DISEASE - INTERACTION OF APOLIPOPROTEIN-E GENOTYPE, FAMILYHISTORY OF DEMENTIA, GENDER, EDUCATION, ETHNICITY, AND AGE-OF-ONSET

We evaluated 197 patients with predominantly late-onset Alzheimer's di sease (AD) who belonged to several ethnic groups and analyzed the rela tionship of age of onset of AD to the presence or absence of several r isk factors in this entire group of patients. The apolipoprotein E (ap oE) epsilon 4 allele frequency, which was 29% in all patients (compare d with the reported population mean of 13.7%, p < 0.001, did not vary significantly between ethnic groups but declined significantly with in creasing age. The apoE epsilon 2 allele frequency was 3%, compared wit h the reported population mean of 7.4% (p = 0.001). The frequency of a positive family history of dementia in first-degree relatives (FH+) ( overall 45%) did not vary significantly between ethnic groups. ApoE ep silon 4-positive (epsilon 4+) patients tended to have a higher FH+ rat e (58%) than apoE epsilon 4-negative (epsilon 4-) patients (40%) (p = 0.02). When the potential risk factors of gender, education, FH+ statu s, and epsilon 4+ status were examined together in a multiple linear-r egression analysis, FH+ and epsilon 4+ status (but not gender or educa tion) were significant (they were both associated with an earlier age of onset of AD). In a post-hoc analysis, we found a reduced age of ons et in women, but not men, who were both FH+ and epsilon 4+. Additional ly, those probands who were epsilon 4+ were more likely to inherit the disease from their mothers than their fathers. The mechanism by which epsilon 4+ and FH+ status operate as risk factors may be by their eff ect on the age of onset of AD.