The cholesteryl ester transfer protein (CETP) gene and the risk of Alzheimer's disease.

Like the apolipoprotein E (APOE) gene, the most common genetic determinant for Alzheimer's disease (AD), the cholesteryl ester transfer protein (CETP) is involved in lipid metabolism. We studied the I405V polymorphism of the CETP gene in relation to AD. We genotyped 544 AD cases and 5,404 controls from the Rotterdam study, using a TaqMan allelic discrimination assay. Odds ratios (ORs) for AD were estimated using logistic regression analysis. CETP VV carriers showed significantly increased high-density lipoprotein levels compared to the IV and II carriers. In the overall analysis of AD, the risk of disease for the VV carriers of the CETP polymorphism was non-significantly increased compared to II carriers OR(VV) = 1.33, 95% confidence interval (CI) 0.96-1.90 p = 0.08). In those without the APOE4 allele, the risk of AD for VV carriers was increased 1.67-fold (95% CI 1.11-2.52, p = 0.01). The difference in the relationship between CETP and AD between APOE4 carriers and APOE4 non-carriers was statistically significant (p for interaction = 0.04). Our results suggest that the VV genotype of the I405V polymorphism of the CETP gene increases the risk of AD in the absence of the APOE4 allele, probably through a cholesterol metabolism pathway in the brain.