Interactions of apolipoprotein E genotype, total cholesterol level, age, and sex in prediction of Alzheimer's disease: a case-control study

Neurology. 1995 Jun;45(6):1092-6. doi: 10.1212/wnl.45.6.1092.


Objective: The joint effects of total cholesterol (TC) levels and the APOE genotype in Alzheimer's disease (AD) were evaluated because of previous reports that the APOE locus epsilon 4 allele was associated with both late-onset AD and elevated TC.

Design: Logistic regression was used to determine the effects of the APOE genotype, TC, age, and sex on prediction of AD in a community-based study of 206 cases and 276 controls.

Results: The relationship of the APOE genotype and AD was dependent on TC, age, and sex. However, current TC level does not fully explain the epsilon 4-Alzheimer's disease association. Affected men with higher TC and age under 80 years had the highest epsilon 4 allele frequencies. The epsilon 4 frequency declined significantly with age.

Significance: A pathologic role of higher TC or cholesterol-based differential survival of epsilon 4-carrying individuals may be involved in the relationship of the epsilon 4 allele with AD. The observed association of the APOE genotype and AD is expected to depend on the age, sex, and TC distributions of a given sample.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alleles
  • Alzheimer Disease / epidemiology
  • Alzheimer Disease / genetics*
  • Alzheimer Disease / metabolism*
  • Apolipoprotein E4
  • Apolipoproteins E / genetics*
  • Case-Control Studies
  • Cholesterol / analysis*
  • Female
  • Genotype
  • Humans
  • Male
  • Sex Characteristics


  • Apolipoprotein E4
  • Apolipoproteins E
  • Cholesterol