Tan Lin, Wang Hui-Fu, Tan Meng-Shan, Tan Chen-Chen, Zhu Xi-Chen, Miao Dan, Yu Wan-Jiang, Jiang Teng, Tan Lan, Yu Jin-Tai
College of Medicine and Pharmaceutics, Ocean University of China, China.
Department of Neurology, Qingdao Municipal Hospital, Nanjing Medical University, Qingdao, China.
Sci Rep. 2016 May 27;6:26027. doi: 10.1038/srep26027.
The Clusterin (CLU) gene, also known as apolipoprotein J (ApoJ), is currently the third most associated late-onset Alzheimer's disease (LOAD) risk gene. However, little was known about the possible effect of CLU genetic variants on AD pathology in brain. Here, we evaluated the interaction between 7 CLU SNPs (covering 95% of genetic variations) and the role of CLU in β-amyloid (Aβ) deposition, AD-related structure atrophy, abnormal glucose metabolism on neuroimaging and CSF markers to clarify the possible approach by that CLU impacts AD. Finally, four loci (rs11136000, rs1532278, rs2279590, rs7982) showed significant associations with the Aβ deposition at the baseline level while genotypes of rs9331888 (P = 0.042) increased Aβ deposition. Besides, rs9331888 was significantly associated with baseline volume of left hippocampus (P = 0.014). We then further validated the association with Aβ deposition in the AD, mild cognitive impairment (MCI), normal control (NC) sub-groups. The results in sub-groups confirmed the association between CLU genotypes and Aβ deposition further. Our findings revealed that CLU genotypes could probably modulate the cerebral the Aβ loads on imaging and volume of hippocampus. These findings raise the possibility that the biological effects of CLU may be relatively confined to neuroimaging trait and hence may offer clues to AD.
簇集素（CLU）基因，也被称为载脂蛋白J（ApoJ），目前是与晚发性阿尔茨海默病（LOAD）风险关联度排名第三的基因。然而，关于CLU基因变异对大脑中AD病理的可能影响却知之甚少。在此，我们评估了7个CLU单核苷酸多态性（SNP，涵盖95%的基因变异）之间的相互作用，以及CLU在β淀粉样蛋白（Aβ）沉积、AD相关结构萎缩、神经影像学上的异常葡萄糖代谢和脑脊液标志物方面的作用，以阐明CLU影响AD的可能途径。最后，四个位点（rs11136000、rs1532278、rs2279590、rs7982）在基线水平与Aβ沉积显示出显著关联，而rs9331888的基因型增加了Aβ沉积（P = 0.042）。此外，rs9331888与左侧海马体的基线体积显著相关（P = 0.014）。然后，我们在AD、轻度认知障碍（MCI）、正常对照（NC）亚组中进一步验证了与Aβ沉积的关联。亚组结果进一步证实了CLU基因型与Aβ沉积之间的关联。我们的研究结果表明，CLU基因型可能会在影像学上调节大脑的Aβ负荷以及海马体体积。这些发现增加了一种可能性，即CLU的生物学效应可能相对局限于神经影像学特征，从而可能为AD提供线索。
