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Cholesterol, APOE genotype, and Alzheimer disease

An epidemiologic study of Nigerian Yoruba

From the Departments of Psychiatry (K.H., J.D., V.S.-G., F.W.U., H.H.), Pathology (J.M.), Biochemistry and Molecular Biology (M.D.), and Neurology (R.E.), Division of Biostatistics (S.G., J.S.), and Regenstrief Institute, Inc. (H.H.), Indiana University School of Medicine, Indianapolis; and Departments of Medicine (A.O.) and Psychiatry (O.B., O.G.), College of Medicine, University of Ibadan, Ibadan, Nigeria.

Address correspondence and reprint requests to Dr. Kathleen S. Hall, Department of Psychiatry, Indiana University School of Medicine, 1111 West Tenth Street, PB A319, Indianapolis, IN 46202; e-mail: khall{at}iupui.edu

Objective: To examine the relationship between cholesterol and other lipids, APOE genotype, and risk of Alzheimer disease (AD) in a population-based study of elderly Yoruba living in Ibadan, Nigeria.

Methods: Blood samples and clinical data were collected from Yoruba study participants aged 70 years and older (N = 1,075) as part of the Indianapolis-Ibadan Dementia Project, a longitudinal epidemiologic study of AD. Cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL), and triglyceride levels were measured in fasting blood samples. DNA was extracted and APOE was genotyped. Diagnoses of AD were made by consensus using National Institute of Neurologic Disorders/Stroke-Alzheimer's Disease and Related Disorders Association criteria.

Results: Logistic regression models showed interaction after adjusting for age and gender between APOE-4 genotype and biomarkers in the risk of AD cholesterol*genotype (p = 0.022), LDL*genotype (p= 0.018), and triglyceride*genotype (p = 0.036). Increasing levels of cholesterol and LDL were associated with increased risk of AD in individuals without the APOE-4 allele, but not in those with APOE-4. There was no significant association between levels of triglycerides and AD risk in those without APOE-4.

Conclusions: There was a significant interaction between cholesterol, APOE-4, and the risk of Alzheimer disease (AD) in the Yoruba, a population that has lower cholesterol levels and lower incidence rates of AD compared to African Americans. APOE status needs to be considered when assessing the relationship between lipid levels and AD risk in population studies.

Supported by grant RO1AGO9956-14, The Indianapolis-Ibadan Dementia Project from the National Institute on Aging.

Disclosure: The authors report no conflicts of interest.

Received July 20, 2005. Accepted in final form October 10, 2005.

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