Convergent and divergent effects of apolipoprotein E ε4 and ε2 alleles on amygdala functional networks in nondemented older adults
Convergent and divergent effects of apolipoprotein E ε4 and ε2 alleles on amygdala functional networks in nondemented older adults
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DOI：
10.1016/j.neurobiolaging.2017.02.013
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发表时间：
2017-06-01
影响因子：
4.2
通讯作者：
Zhang, Zhijun
中科院分区：
文献类型：
--
作者：
Gong, Liang;Shu, Hao;Zhang, Zhijun
传统上，在阿尔茨海默病的背景下，载脂蛋白E β 2（APOE β 2）等位基因是保护性因素，而APOE β 4等位基因是破坏性因素。然而，这种反向关系最近受到了挑战，APOE基因型对阿尔茨海默病影响的神经机制仍不清楚。采用静息态功能磁共振成像（FMRI）技术，对84例遗忘型轻度认知功能障碍患者和124例认知功能正常成人的APOE基因型和年龄对杏仁核功能连接（AFC）网络的影响进行了研究。结果表明，APOE等位基因<$2和APOE等位基因<$4在右AFC网络中产生会聚效应，而在左AFC网络中产生发散效应。随着年龄的增长，APOE β 2携带者表现出稳定的AFC，而APOE β 4携带者在所有参与者中表现出降低的AFC。此外，中介分析显示，连接强度调节APOE基因型和年龄对遗忘型轻度认知功能障碍患者认知功能的影响。我们的研究结果表明，APOE等位基因的APOE E12和APOE E14产生收敛和发散的脑功能的拓扑效应。(C)2017爱思唯尔公司All rights reserved.
Traditionally, in the context of Alzheimer's disease, the apolipoprotein E epsilon 2 (APOE epsilon 2) allele is a protective factor and the APOE epsilon 4 allele is a destructive factor. However, this inverse relationship has recently been challenged, and the neural mechanisms underlying the effects of APOE genotype on Alzheimer's disease remain unclear. A resting-state functional magnetic resonance imaging study was conducted to investigate the effects of APOE genotype and age on amygdala functional connectivity (AFC) networks in 84 patients with amnestic mild cognitive impairment and 124 cognitively normal order adults. The results indicated that the APOE epsilon 2 and APOE epsilon 4 alleles produced convergent effects in the right AFC network but divergent effects in the left AFC network. As age increased, APOE epsilon 2 carriers showed stable AFC, whereas APOE epsilon 4 carriers exhibited decreased AFC in all participants. Furthermore, mediation analysis revealed that connectivity strength regulates the effects of APOE genotype and age on cognitive function in amnestic mild cognitive impairment patients. Our findings suggest that the APOE epsilon 2 and APOE epsilon 4 alleles produce both convergent and divergent topological effects on brain function. (C) 2017 Elsevier Inc. All rights reserved.