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The Apolipoprotein E E4 Allele and Sex-Specific Risk of Alzheimer's Disease

Elizabeth H. Corder, PhD; Ann M. Saunders, PhD; Warren J. Strittmatter, MD; Don E. Schmechel, MD; P. C. Gaskell Jr, PA-C; A. D. Roses, MD; M. A. Pericak-Vance, PhD; G. W. Small, MD; J. L. Haines, PhD
JAMA. 1995;273(5):373-374. doi:10.1001/jama.1995.03520290025013.
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To the Editor.  —Recently, Dr Payami and colleagues proposed a difference in Alzheimer's disease (AD) risk between men and women who have one copy of the apolipoprotein E (apo E) E4 allele.1 Specifically, they suggested that men with no or one copy of E4 (the E2/E2, E2/E3, E3/E3, E2/E4, and E3/E4 genotypes) have a decreased risk of AD compared with men with two copies (the E4/E4 genotype), while women with no copy of E4 have a decreased risk of AD compared with those with one or two copies. Our studies do not suggest this sex-specific pattern of risk.2,3 We find instead that risk of AD, both familial and sporadic (ie, no family history), increases with the number of E4 alleles in men and women.The E4 gene dose effect was initially found in 234 members of 42 AD families older than 60 years and can be seen when


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