Tsai Alex, Huang Chu-Chung, Yang Albert C, Liu Mu-En, Tu Pei-Chi, Hong Chen-Jee, Liou Ying-Jay, Chen Jin-Fan, Lin Ching-Po, Tsai Shih-Jen
Department of Psychiatry, Taipei Veterans General Hospital, Taipei, ROC.
Dement Geriatr Cogn Dis Extra. 2012 Jan;2(1):632-7. doi: 10.1159/000345980. Epub 2012 Dec 15.
β-Site amyloid precursor protein (APP)-cleaving enzyme 1 (BACE1) is a biological and positional candidate gene for Alzheimer's disease (AD). Previous studies found that BACE1-null mice had impaired performance on cognition and neurodegeneration during the aging process. Additionally, a synonymous polymorphism of BACE1 (rs638405) in exon 5 has been reported to be associated with risk for AD. We hypothesized that this BACE1 gene variant might influence regional brain volumes and cognitive tests in normal individuals.
Participants were 330 normal volunteers between 21 and 92 years of age (mean age 56.3 ± 22.0 years; 191 males, 139 females). Cognitive tests (the Mini-Mental State Examination and Digit Spans), magnetic resonance imaging, and genotyping of BACE1 rs638405 were examined for each subject. The differences in regional gray matter (GM) volumes between G homozygotes and C-allele carriers were tested using optimized voxel-based morphometry.
Compared to C-allele carriers, G homozygotes exhibited significantly larger GM volumes in the left cerebellar culmen and right cerebellar lingual area, but no significant differences on cognitive function tests.
The findings suggest that the BACE1 rs638405 polymorphism may affect cerebellar morphology, but not cognitive function in healthy humans.
β-淀粉样前体蛋白（APP）裂解酶1（BACE1）是阿尔茨海默病（AD）的一个生物学和定位候选基因。先前的研究发现，BACE1基因敲除小鼠在衰老过程中认知能力受损且出现神经退行性变。此外，据报道，外显子5中BACE1的一个同义多态性（rs638405）与AD风险相关。我们推测这种BACE1基因变异可能会影响正常个体的脑区体积和认知测试。
参与者为330名年龄在21至92岁之间的正常志愿者（平均年龄56.3±22.0岁；男性191名，女性139名）。对每位受试者进行认知测试（简易精神状态检查表和数字广度测试）、磁共振成像以及BACE1 rs638405基因分型。使用优化的基于体素的形态测量法检测G纯合子和C等位基因携带者之间脑区灰质（GM）体积的差异。
与C等位基因携带者相比，G纯合子在左侧小脑山顶和右侧小脑舌叶区域的GM体积显著更大，但在认知功能测试中无显著差异。
研究结果表明，BACE1 rs638405多态性可能会影响健康人的小脑形态，但不影响认知功能。
