Interactions of apolipoprotein E genotype, total cholesterol level, age, and sex in prediction of Alzheimer's disease

Objective The joint effects of total cholesterol (TC) levels and the APOE genotype in Alzheimer9s disease (AD) were evaluated because of previous reports that the APOE locus ϵ4 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 ϵ4-Alzheimer9s disease association. Affected men with higher TC and age under 80 years had the highest ϵ4 allele frequencies. The ϵ4 frequency declined significantly with age. Significance A pathologic role of higher TC or cholesterol-based differential survival of ϵ4-carrying individuals may be involved in the relationship of the ϵ4 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.