CETP polymorphisms associate with brain structure, atrophy rate, and Alzheimer’s disease risk in an APOE-dependent manner

Department of Neurosciences, University of California, San Diego, CA, USA.
Brain Imaging and Behavior (Impact Factor: 4.6). 09/2011; 6(1):16-26. DOI: 10.1007/s11682-011-9137-0
Source: PubMed


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.

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    ABSTRACT: Common polymorphisms of the Cholestryl Ester Transfer Protein (CETP) gene may predict lower risk of cognitive decline. We investigated the association of cognitive function with CETP genotype in a population-based cohort of 4135 persons aged 35-82 years. Cognitive function was measured with the Ruff Figural Fluency Test (RFFT; worst score, 0 points; best score, 175 points) and CETP I405V and Taq1B genotypes were determined by polymerase chain reaction. RFFT score was not associated with I405V genotype in persons aged 35-64 years. Remarkably, beyond age 65, homozygous valine carriers had higher RFFT scores than heterozygous carriers and noncarriers: RFFT (SD), 52 (21), 49 (18), and 47 (17) points, respectively (p = 0.005). There also was a statistically significant interaction between I405V genotype and age. Beyond age 65, the difference between homozygous valine carriers and noncarriers increased by 0.11 point per year (p = 0.005). RFFT score was not associated with Taq1B genotype. In conclusion, CETP I405V valine homozygosity was associated with better cognitive function in persons aged 65 years or older.
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