Impacts of PICALM and CLU variants associated with Alzheimer’s disease on the functional connectivity of the hippocampus in healthy young adults
Impacts of PICALM and CLU variants associated with Alzheimer’s disease on the functional connectivity of the hippocampus in healthy young adults
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DOI：
10.1007/s00429-014-0738-4
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发表时间：
2014-02
影响因子：
3.1
通讯作者：
Peng Zhang;W. Qin;Dawei Wang;Bing Liu;Yunting Zhang;T. Jiang;Chunshui Yu
中科院分区：
文献类型：
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作者：
Peng Zhang;W. Qin;Dawei Wang;Bing Liu;Yunting Zhang;T. Jiang;Chunshui Yu
PICALM rs3851179和CLU rs 11136000最近与阿尔茨海默病（AD）相关。研究这些遗传变异对海马静息状态功能连接（rsFC）的影响可能为AD发病机制提供新的见解。我们研究了这两种遗传变异对283名健康年轻人海马rsFC的主要影响和相互作用。海马在默认模式网络中呈现阳性rsFC，在额顶网络中呈现阴性rsFC。与AA携带者相比，PICALM G等位基因携带者的rsFC阴性较弱，而CLU-CC携带者的rsFC阳性和阴性较T等位基因携带者强。PICALM和CLU在海马负性rsFC上存在复杂的交互作用。此外，我们发现一个等位基因依赖性的影响，CLU海马连接时，加性遗传模型被应用到CLU。即使在控制个体ApoE状态后，这些效应中的大多数仍然显著。我们的研究结果表明，PICALM和CLU风险基因型对健康年轻受试者的海马rsFC产生不同的影响。在研究这两种遗传变异对大脑的影响时，应该考虑PICALM和CLU之间复杂的相互作用。
PICALM rs3851179 and CLU rs11136000 have been recently associated with Alzheimer’s disease (AD). Investigating the effects of these genetic variants on the resting-state functional connectivity (rsFC) of the hippocampus may provide new insight into AD pathogenesis. We investigated the main effects and interactions of these two genetic variants on hippocampal rsFC in 283 healthy young adults. The hippocampus showed positive rsFC with the default mode network and negative rsFC with the fronto-parietal network. Risk PICALM G-allele carriers showed weaker negative rsFC compared with AA carriers, whereas risk CLU-CC carriers exhibited stronger positive and negative rsFC than T-allele carriers. There existed complex interactions between PICALM and CLU on the negative rsFC of the hippocampus. Moreover, we found an allele-dependent effect of CLU on hippocampal connectivity when an additive genetic model was applied to CLU. Most of these effects remained significant even after controlling for individual ApoE status. Our results suggest that PICALM and CLU risk genotypes exert differential impacts on the hippocampal rsFC in healthy young subjects. The complex interactions between PICALM and CLU should be considered when investigating the impact of these two genetic variants on the brain.