Cholesterol, APOE genotype, and Alzheimer disease

Abstract

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-ε4 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-ε4 allele, but not in those with APOE-ε4. There was no significant association between levels of triglycerides and AD risk in those without APOE-ε4.Conclusions-There was a significant interaction between cholesterol, APOE-ε4, 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.The APOE-ε4 allele is a risk factor for Alzheimer disease (AD) in most populations. 1 The association between APOE-ε4 and AD for African Americans is less clear with some studies reporting no association 2 and others a weak association, 3 perhaps confined to the homozygous state. 4 We found no association between possession of the APOE-ε4 allele and AD in Yoruba residing in Nigeria. 5 There is increasing evidence that cholesterol plays a role in AD pathology, perhaps through its effects on amyloid deposition. 6 We have previously reported a significant interaction between APOE-ε4, cholesterol, and AD in African Americans in whom increasing We report on the interaction between APOE-ε4, cholesterol, and other lipids on the risk of AD in a population-based cohort of Yoruba who were evaluated as part of the IndianapolisIbadan Dementia Project. MethodsSince 1992, we have been conducting a comparative, community-based epidemiologic study of prevalence rates, incidence rates, and risk factors for AD in populations of African origin, elderly African Americans in Indianapolis, IN, and Yoruba living in Ibadan, Nigeria. Study participants have been evaluated at approximately 36-month intervals; this report focuses on the Ibadan site, which is located in the southwestern part of Nigeria where the predominant ethnic group is the Yoruba.In 2001, we conducted a two-stage study in which survivors of the 1992 cohort were ...

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