Genetics
Cache County Study links CETP I405V valine allele to slower cognitive decline in 4,486 older adults (Neurobiol Aging 2015)
Original title: Population-based analysis of cholesteryl ester transfer protein identifies association between I405V and cognitive decline: the Cache County Study
Because CETP regulates cellular cholesterol and cholesterol is implicated in late-onset Alzheimer's disease (LOAD), researchers tested whether the CETP I405V variant (rs5882) affects cognition, genotyping 4486 subjects with up to 12 years of longitudinal cognitive assessment in the Cache County Study. Each additional valine allele was associated with an average 0.6-point-per-year slower rate of cognitive decline (p < 0.011). However, no association was found between CETP I405V and LOAD status (p < 0.28). The authors conclude CETP I405V is associated with preserved cognition over time but not with LOAD risk itself.
Original abstract
Cholesterol has been implicated in the pathogenesis of late-onset Alzheimer's disease (LOAD) and the cholesteryl ester transfer protein (CETP) is critical to cholesterol regulation within the cell, making CETP an Alzheimer's disease candidate gene. Several studies have suggested that CETP I405V (rs5882) is associated with cognitive function and LOAD risk, but findings vary and most studies have been conducted using relatively small numbers of samples. To test whether this variant is involved in cognitive function and LOAD progression, we genotyped 4486 subjects with up to 12 years of longitudinal cognitive assessment. Analyses revealed an average 0.6-point decrease per year in the rate of cognitive decline for each additional valine (p < 0.011). We failed to detect the association between CETP I405V and LOAD status (p < 0.28). We conclude that CETP I405V is associated with preserved cognition over time but is not associated with LOAD status.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.