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.