Genetics
CETP polymorphisms are linked to brain structure and Alzheimer's risk in an APOE-dependent manner (Brain Imaging Behav 2012)
Original title: CETP polymorphisms associate with brain structure, atrophy rate, and Alzheimer's disease risk in an APOE-dependent manner
Using data from 188 elderly controls and 318 Alzheimer's disease or mild cognitive impairment subjects in the Alzheimer's Disease Neuroimaging Initiative cohort, researchers tested whether CETP variants I405V and C-629A, previously and disputably linked to enhanced cognition, affect brain structure. Associations depended on APOE e4 carrier status: in APOE e4 carriers, the V and A alleles, which decrease CETP and increase HDL, were associated with greater baseline cortical thickness and less 12-month atrophy in the medial temporal lobe. In APOE e4 non-carriers, the opposite pattern held, with the I allele, which increases CETP and decreases HDL, associated with greater baseline thickness, less atrophy and lower dementia risk, suggesting CETP contributes to brain structure and dementia susceptibility in an APOE-dependent manner.
Original abstract
Two alleles in cholesteryl ester transfer protein (CETP) gene polymorphisms have been disputably linked to enhanced cognition and decreased risk of Alzheimer's disease (AD): the V and A alleles of I405V and C-629A. This study investigates whether these polymorphisms affect brain structure in 188 elderly controls and 318 AD or mild cognitive impairment (MCI) subjects from the Alzheimer's Disease Neuroimaging Initiative cohort. Nominally signficant associations were dependent on APOE ε4 carrier status. In APOE ε4 carriers, the V and A alleles, both of which decrease CETP and increase HDL, associated with greater baseline cortical thickness and less 12-month atrophy in the medial temporal lobe. Conversely, in APOE ε4 non-carriers, the I allele, which increases CETP and decreases HDL, associated with greater baseline thickness, less atrophy and lower risk of dementia. These results suggest CETP may contribute to the genetic variability of brain structure and dementia susceptibility in an APOE-dependent manner.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 19 August 2026. Methods.