The apolipoprotein E gene affects the three-year trajectories of compensatory neural processes in the left-lateralized hippocampal network
The apolipoprotein E gene affects the three-year trajectories of compensatory neural processes in the left-lateralized hippocampal network
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DOI：
10.1007/s11682-016-9623-5
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发表时间：
2017-10
影响因子：
3.2
通讯作者：
Q. Ye;F. Su;H. Shu;L. Gong;C. Xie;Zhijun Zhang;F. Bai
中科院分区：
文献类型：
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作者：
Q. Ye;F. Su;H. Shu;L. Gong;C. Xie;Zhijun Zhang;F. Bai
先前的横断面研究调查了载脂蛋白E（ApoE）ε4状态对海马网络的影响，结果不一致。衰老是阿尔茨海默病（AD）的一个众所周知的危险因素，并可能与ApoE相关的脆弱性强烈相互作用，影响AD的风险。然而，没有纵向数据已公布的ApoE基因型和海马网络老化的相互作用。51名遗忘型轻度认知功能障碍（aMCI）患者和64名匹配的认知功能正常的老年受试者在基线和35个月随访时接受静息状态fMRI扫描和神经心理学测试。采用混合协方差分析，以ApoE基因型、时间点和疾病作为固定因素，控制年龄、性别和受教育年限，分析海马静息状态功能连接（FC）数据。值得注意的是，ε4携带者的左海马和右额叶之间的FC在正常受试者中纵向增加，但在aMCI患者中减少，而非携带者的FC在正常受试者中保持不变，但在aMCI患者中增加。具体而言，纵向增加海马FC与右额下回正相关的变化，情节记忆测试分数在非携带者与aMCI。ApoE基因型、衰老和疾病之间的相互作用表明，衰老应被视为ApoE基因型对AD表型变异影响的关键调节因子。这些发现还表明，代偿性神经过程在遗传高风险个体中加速，但随后可能随着认知障碍的发作而耗尽。
Previous cross-sectional studies that investigated the effects of apolipoprotein E (ApoE) ε4 status on hippocampal networks have shown inconsistent results. Aging is a well-known risk factor for Alzheimer’s disease (AD) and could strongly interact with ApoE-related vulnerabilities to affect AD risk. However, no longitudinal data have been published regarding the interaction of the ApoE genotype and aging on hippocampal networks. Fifty-one patients with amnestic-type mild cognitive impairment (aMCI) and 64 matched cognitively normal elderly subjects underwent resting-state fMRI scans and neuropsychological tests at baseline and at a 35-month follow-up. Hippocampal resting-state functional connectivity (FC) data were analyzed utilizing a mixed analysis of covariance with ApoE genotype, time points and disease as fixed factors, controlling for age, sex and years of education. The notable finding was that the FC between the left hippocampus and right frontal regions for ε4 carriers longitudinally increased in the normal subjects, but decreased in aMCI patients, whereas the FC for non-carriers was maintained in normal subjects but increased in aMCI patients. Specifically, the longitudinal increases in hippocampal FC with the right inferior frontal gyrus were positively correlated with the changes in episodic memory test scores in non-carriers with aMCI. The interaction between the ApoE genotype, aging and disease suggested that aging should be considered a key regulator of the impact of the ApoE genotype on the phenotypic variants of AD. These findings also demonstrated that compensatory neural processes were accelerated in genetically high risk individuals, but could be subsequently exhausted with the onset of cognitive impairment.