Functional network endophenotypes unravel the effects of apolipoprotein E epsilon 4 in middle-aged adults.
Functional network endophenotypes unravel the effects of apolipoprotein E epsilon 4 in middle-aged adults.
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DOI：
10.1371/journal.pone.0055902
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Li SJ
中科院分区：
文献类型：
--
作者：
Goveas JS;Xie C;Chen G;Li W;Ward BD;Franczak MB;Jones JL;Antuono PG;Li SJ
载脂蛋白E-ε4（APOE-ε4）加重认知健康成人的记忆衰退、结构体积损失和脑淀粉样蛋白沉积。我们研究了APOE-ε4携带者是否会在固有认知网络中表现出破坏，包括默认模式（DMN），执行控制（ECN）和显着性（SN）网络，相对于中年健康成人的非携带者;以及这些网络中的功能连接（Fc）改变与情节记忆表现的相关程度。应用静息态功能连接MRI（R-fMRI）检测20例APOE-ε4携带者和26例非携带者的DMN、ECN和SN Fc的差异。进行多元线性回归分析，以确定所有受试者在三种静息状态网络中的情景记忆表现和Fc差异之间的关系。携带者和非携带者的人口统计学和神经心理学特征以及灰质体积没有显着差异。虽然大多数DMN和ECN功能连接性减弱，但在ε4载体中的SN中发现与DMN结构的连接增强。DMN和ECN的改变与情景记忆表现相关。在没有认知能力下降和灰质萎缩的情况下，在具有AD遗传风险的中年个体中观察到与认知有关的脑网络中的显著Fc差异。前瞻性研究对于阐明R-fMRI技术作为预测健康APOE-ε4携带者从正常向早期AD转化的生物标志物的潜力至关重要。
Apolipoprotein E-ε4 (APOE-ε4) accentuates memory decline, structural volume loss and cerebral amyloid deposition in cognitively healthy adults. We investigated whether APOE-ε4 carriers will show disruptions in the intrinsic cognitive networks, including the default mode (DMN), executive control (ECN) and salience (SN) networks, relative to noncarriers in middle-aged healthy adults; and the extent to which episodic-memory performance is related to the altered functional connectivity (Fc) in these networks. Resting-state functional connectivity MRI (R-fMRI) was used to measure the differences in the DMN, ECN and SN Fc between 20 APOE-ε4 carriers and 26 noncarriers. Multiple linear regression analyses were performed to determine the relationship between episodic-memory performance and Fc differences in the three resting-state networks across all subjects. There were no significant differences in the demographic and neuropsychological characteristics and the gray-matter volumes in the carriers and noncarriers. While mostly diminished DMN and ECN functional connectivities were seen, enhanced connections to the DMN structures were found in the SN in ε4 carriers. Altered DMN and ECN were associated with episodic memory performance. Significant Fc differences in the brain networks implicated in cognition were seen in middle-aged individuals with a genetic risk for AD, in the absence of cognitive decline and gray-matter atrophy. Prospective studies are essential to elucidate the potential of R-fMRI technique as a biomarker for predicting conversion from normal to early AD in healthy APOE-ε4 carriers.