APOE-MS4A genetic interactions are associated with executive dysfunction and network abnormality in clinically mild Alzheimer's disease
APOE-MS4A genetic interactions are associated with executive dysfunction and network abnormality in clinically mild Alzheimer's disease
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DOI：
10.1016/j.nicl.2018.101621
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发表时间：
2019-01-01
影响因子：
4.2
通讯作者：
Chang, Chiung-Chih
中科院分区：
文献类型：
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作者：
Chang, Ya-Ting;Mori, Etsuro;Chang, Chiung-Chih
研究目的：尽管跨膜蛋白4A（MS 4A）（rs670139）和其他几个易感基因的单核苷酸多态性显示出对阿尔茨海默病（AD）风险的交互作用，但关于载脂蛋白E（APOE）与MS 4A（rs670139）对认知表现的交互作用知之甚少，并且潜在的发病机制尚不清楚。本研究旨在探讨APOE-MS 4A（rs670139）相互作用对认知能力、皮层体积和脑网络功能连接（FC）的影响。主要结果：认知能力在每个基因型组中均有特征，并在正常对照组和每个基因型组的患者之间进行比较。证明了APOE-MS 4A相互作用对记忆和执行功能评分、皮质体积和脑网络中的FC的影响。在执行控制网络（ECN）中观察到APOE-MS 4A相互作用对FC的显著影响。（T最大值= 4.99，错误发现率校正p < .001），计算得分（F3，87 = 6.218; p = 0.015），以及前额叶（F3，87 = 4.374; p = 0.039）和眶额皮质（F3，87 = 6.022; p = 0.016）的体积。计算得分与每个额叶体积（cc）（rho = 0.304; p = 0.004）和ECN中遗传相互作用相关的FC（rho = 0.282; p = 0.008）相关。基因型的差异影响计算得分和每个额叶体积（cc）之间的关系。主要结论：这些结果表明，在ECN FC的遗传互作效应可能有助于在AD的计算能力的APOE-MS 4A的交互作用的致病机制。
Purpose of the research: Although single nucleotide polymorphisms of membrane-spanning 4A (MS4A) (rs670139) and several other susceptibility genes have shown interaction effects on the risk of Alzheimer's disease (AD), little is known about the interaction effects of apolipoprotein E (APOE) with MS4A (rs670139) on cognitive performances, and the underlying pathogenesis is unclear. The study aimed to investigate the APOE-MS4A (rs670139) interaction effects on cognitive performances, cortical volumes, and functional connectivity (FC) in brain networks.Principal results: Cognitive performances were characterized in each genotypic group, and were compared between normal controls and patients in each genotypic group. APOE-MS4A interaction effects on memory and executive function scores, cortical volumes, and FC in brain networks were demonstrated. Significant effects of APOE-MS4A interactions on FC were observed in executive control network (ECN) (T maxima = 4.99, false discovery rate-corrected p < .001), the calculation score (F3, 87 = 6.218; p = .015), and the volume in prefrontal (F3, 87 = 4.374; p = .039) and orbitofrontal cortices (F3, 87 = 6.022; p = .016). The calculation score was correlated with each frontal volume (cc) (rho = 0.304; p = .004) and genetic interaction-associated FC in ECN (rho = 0.282; p = .008). Variations in genotypes affected the relationship between the calculation score and each frontal volume (cc).Major conclusions: These findings indicate that the genetic interaction effects on FC in ECN might contribute to pathogenic mechanisms underlying the interaction effects of APOE-MS4A on calculation ability in AD.