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

Academic Article


  • 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. © 1996 by The American Society of Human Genetics. All rights reserved.
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    Author List

  • Payami H; Zareparsi S; Montee KR; Sexton GJ; Kaye JA; Bird TD; Yu CE; Wijsman EM; Heston LL; Litt M
  • Start Page

  • 803
  • End Page

  • 811
  • Volume

  • 58
  • Issue

  • 4