Alzheimer's disease: Interaction of apolipoprotein E genotype, family history of dementia, gender, education, ethnicity, and age of onset

R. Duara, W. W. Barker, R. Lopez-Alberola, D. A. Loewenstein, L. B. Grau, D. Gilchrist, S. Sevush, P. H. St. George-Hyslop

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114 Scopus citations


We evaluated 197 patients with predominantly late-onset Alzheimer's disease (AD) who belonged to several ethnic groups and analyzed the relationship of age of onset of AD to the presence or absence of several risk factors in this entire group of patients. The apolipoprotein E (apoE) ε4 allele frequency, which was 29% in all patients (compared with the reported population mean of 13.7%, p < 0.001, did not vary significantly between ethnic groups but declined significantly with increasing age. The apoE ε2 allele frequency was 3%, compared with 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 ε4-positive (ε4+) patients tended to have a higher FH+ rate (58%) than apoE ε4-negative (ε4-) patients (40%) (p = 0.02). When the potential risk factors of gender, education, FH+ status, and ε4+ status were examined together in a multiple linear-regression analysis, FH+ and ε4+ status (but not gender or education) 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 onset in women, but not men, who were both FH+ and ε4+. Additionally, those probands who were ε4+ were more likely to inherit the disease from their mothers than their fathers. The mechanism by which ε4+ and FH+ status operate as risk factors may be by their effect on the age of onset of AD.

Original languageEnglish (US)
Pages (from-to)1575-1579
Number of pages5
Issue number6
StatePublished - Jun 1996


ASJC Scopus subject areas

  • Clinical Neurology

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