Gender difference in apolipoprotein E - associated risk for familial alzheimer disease: A possible clue to the higher incidence of alzheimer disease in women

Haydeh Payami, Sepideh Zareparsi, Kim R. Montee, Gary J. Sexton, Jeffrey A. Kaye, Thomas D. Bird, Chang En Yu, Ellen M. Wijsman, Leonard L. Heston, Michael Litt, Gerard D. Schellenberg

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194 Scopus citations

Abstract

Late-onset Alzheimer disease (AD) is associated with the Apolipoprotein E (APOE) - ε4 allele. In late-onset familial AD, women have a significantly higher risk of developing the disease than do men. The aim of this study was to determine whether the gender difference in familial AD is a function of APOE genotype. We studied 58 late-onset familial AD kindreds. Kaplan-Meier survival analysis was used to assess genotype-specific distributions of age at onset. Odds ratios were estimated by logistic regression with adjustment for age and by conditional logistic regression with stratification on families. All methods detected a significant gender difference for the ε4 heterozygous genotype. In women, ε4 heterozygotes had higher risk than those without ε4; there was no significant difference between ε4 heterozygotes and ε4 homozygotes. In men, ε4 heterozygotes had lower risk than ε4 homozygotes; there was no significant difference between ε4 heterozygotes and those without ε4. A direct comparison of ε4 heterozygous men and women revealed a significant twofold increased risk in women. We confirmed these results in 15 autopsy-confirmed AD kindreds from the National Cell Repository at Indiana University Alzheimer Disease Center. These observations are consistent with the increased incidence of familial AD in women and may be a critical clue to the role of gender in the pathogenesis of AD.

Original languageEnglish (US)
Pages (from-to)803-811
Number of pages9
JournalAmerican Journal of Human Genetics
Volume58
Issue number4
StatePublished - Dec 1 1996

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ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

Payami, H., Zareparsi, S., Montee, K. R., Sexton, G. J., Kaye, J. A., Bird, T. D., Yu, C. E., Wijsman, E. M., Heston, L. L., Litt, M., & Schellenberg, G. D. (1996). Gender difference in apolipoprotein E - associated risk for familial alzheimer disease: A possible clue to the higher incidence of alzheimer disease in women. American Journal of Human Genetics, 58(4), 803-811.