Genetics
Contradicting earlier reports, the CETP I405V polymorphism is linked to faster cognitive decline and higher Alzheimer's risk in a large US cohort (Aging Cell 2012)
Original title: The CETP I405V polymorphism is associated with an increased risk of Alzheimer's disease
Although prior findings had suggested the CETP I405V polymorphism (rs5882) is associated with slower memory decline and lower dementia risk, researchers used data from two ongoing US epidemiologic clinical-pathologic cohort studies, the Religious Order Study and the Memory and Aging Project, to re-evaluate this association in more than 1300 participants of European ancestry. Contrary to the earlier finding, CETP I405V was associated with a faster rate of cognitive decline over time and an increased risk of incident Alzheimer's disease. This result is consistent with separate autopsy data showing CETP I405V is associated with increased neuritic plaque density, indicating the direction of this genetic effect on dementia risk remains unsettled.
Original 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.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 19 August 2026. Methods.