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From the Division of Medical Genetics, Department of Medicine (Drs. Jarvik and Wijsman), Department of Epidemiology (Dr. Kukull), Division of Neurology, Department of Medicine (Drs. Schellenberg and Yu), Departments of Medicine and Health Services (Dr. Larson), and Department of Biostatistics (Dr. Wijsman), University of Washington Medical Center, Seattle, WA.
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
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
4-Alzheimer's disease association. Affected men with higher TC and age under 80 years had the highest
4 allele frequencies. The
4 frequency declined significantly with age.
Significance A pathologic role of higher TC or cholesterol-based differential survival of
4-carrying individuals may be involved in the relationship of the
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.
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