The CETP I405V polymorphism is associated with an increased risk of Alzheimer's disease

Abstract

The cholesteryl ester transfer protein (CETP) gene plays an essential role in regulating cholesterol homeostasis and is a candidate susceptibility gene for late-onset Alzheimer's disease (AD). Recent finding suggests that the CETP I405V polymorphism (rs5882) is associated with a slower rate of memory decline and a lower risk of incident dementia. Using data from two ongoing epidemiologic clinical-pathologic cohort studies of aging and dementia in the United States, the Religious Order Study and the Memory and Aging Project, we evaluated the association of the CETP I405V polymorphism (rs5882) with cognitive decline and risk of incident AD in more than 1300 participants of European ancestry. Our results suggest that the CETP I405V polymorphism was associated with a faster rather than a slower rate of decline in cognition over time, and an increased risk of incident AD. This finding is consistent with data showing that the CETP I405V is associated with increased neuritic plaque density at autopsy.

Figure 1

Decline of global cognition for groups with different I405V genotype. Estimated mean trajectories of global cognition over time for groups with different I405V genotype, adjusted for baseline age, sex, education and APOE. The dotted line represents a typical subject with valine homozygote (rs5882^V/V), and the solid line refers to the one who had the other genotypes.

Figure 2

Risk of incident AD for groups with different I405V genotype. Estimated cumulative hazard of AD between rs5882^V/V (dotted) and the reference genotypes (solid), adjusted for baseline age, sex, education and APOE. Additional scale for AD free survival was shown on the right axis.