Department of Neurosciences, University of California, San Diego, CA, USA.
Brain Imaging Behav. 2012 Mar;6(1):16-26. doi: 10.1007/s11682-011-9137-0.
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.
载脂蛋白 E4 携带者中，两种等位基因（I405V 的 V 和 A 等位基因，以及 C-629A 的 A 等位基因）均降低胆固醇酯转移蛋白（CETP）水平并增加高密度脂蛋白（HDL），与内侧颞叶的更大基线皮质厚度和更少的 12 个月萎缩有关。相反，在载脂蛋白 E4 非携带者中，增加 CETP 并降低 HDL 的 I 等位基因与更大的基线厚度、更少的萎缩和更低的痴呆风险有关。这些结果表明，CETP 可能以载脂蛋白 E4 依赖的方式导致大脑结构和痴呆易感性的遗传变异性。
