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The Apolipoprotein Epsilon 4 Allele in Patients with Alzheimer's Disease

Mayeux, Richard Paul; Stern, Yaakov; Ottman, Ruth; Tatemichi, Thomas K.; Tang, Mingxin; Maestre, Gladys; Ngai, Colleen I.; Tycko, Benjamin; Ginsberg, Henry N.

Apolipoproein E (APO-E) binds to the β-amyloid peptide and is present in senile neuritic plaques in Alzheimer's disease (AD). The ε4 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-ε4 was 17.9 (95% confidence interval [CI], 4.6–69.8) and that associated with heterozygosity for APO-ε4 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% CI, 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-ε4 and AD did not differ according to age at onset (<65 vs ≥65), but appeared to vary across the 3 ethnic groups investigated (black, Hispanic, and white). Our data confirm the association between AD and APO-ε4 and support the hypothesis that the APO-ε4 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-ε4 in the elderly warrants further investigation.

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Also Published In

Title
Annals of Neurology
DOI
https://doi.org/10.1002/ana.410340527

More About This Work

Academic Units
Neurology
Published Here
February 24, 2018
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