Disrupted Functional and Structural Networks in Cognitively Normal Elderly Subjects with the APOE ε4 Allele
Disrupted Functional and Structural Networks in Cognitively Normal Elderly Subjects with the APOE ε4 Allele
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DOI：
10.1038/npp.2014.302
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发表时间：
2015-04-01
影响因子：
7.6
通讯作者：
Reiman, Eric M.
中科院分区：
文献类型：
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作者：
Chen, Yaojing;Chen, Kewei;Reiman, Eric M.
由于载脂蛋白E（APOE）β 4等位基因是散发性阿尔茨海默病（AD）的主要遗传危险因素，AD被认为是一种分离综合征，表现为白色物质（WM）完整性和功能连接（FC）的破坏，阐明认知正常的BMP4携带者的微妙的脑结构和功能网络变化对于识别基于神经成像的敏感生物标志物是必不可少的。并了解临床前AD相关异常的发展。我们首先基于静息态功能磁共振成像构建了功能网络，基于弥散张量成像构建了结构网络。使用这两个网络的全局，局部和节点效率，然后我们检查（i）功能和WM结构网络之间的差异，认知正常的BMP4携带者和非携带者同时，（ii）这些指标作为生物标志物的敏感性，和（iii）它们与行为测量的关系，以及胆固醇水平。对于2004名携带者，我们发现WM和FC的整体效率显著降低，区域FC功能障碍主要集中在内侧颞区，WM网络更广泛。重要的是，右侧海马旁回（PHG. R）是唯一同时发生功能和结构损伤的区域，并且在WM网络中PHG. R的节点效率介导了APOE β 4对记忆功能的影响。最后，胆固醇水平与WM网络的相关性不同于与功能网络的相关性。我们的研究结果表明，EST4特异性异常的结构和功能模式，这可能是潜在的生物标志物，为早期检测疾病的发病前。
As the Apolipoprotein E (APOE) epsilon 4 allele is a major genetic risk factor for sporadic Alzheimer's disease (AD), which has been suggested as a disconnection syndrome manifested by the disruption of white matter (WM) integrity and functional connectivity (FC), elucidating the subtle brain structural and functional network changes in cognitively normal epsilon 4 carriers is essential for identifying sensitive neuroimaging based biomarkers and understanding the preclinical AD-related abnormality development. We first constructed functional network on the basis of resting-state functional magnetic resonance imaging and a structural network on the basis of diffusion tensor image. Using global, local and nodal efficiencies of these two networks, we then examined (i) the differences of functional and WM structural network between cognitively normal epsilon 4 carriers and non-carriers simultaneously, (ii) the sensitivity of these indices as biomarkers, and (iii) their relationship to behavior measurements, as well as to cholesterol level. For epsilon 4 carriers, we found reduced global efficiency significantly in WM and marginally in FC, regional FC dysfunctions mainly in medial temporal areas, and more widespread for WM network. Importantly, the right parahippocampal gyrus (PHG.R) was the only region with simultaneous functional and structural damage, and the nodal efficiency of PHG.R in WM network mediates the APOE epsilon 4 effect on memory function. Finally, the cholesterol level correlated with WM network differently than with the functional network in epsilon 4 carriers. Our results demonstrated epsilon 4-specific abnormal structural and functional patterns, which may potentially serve as biomarkers for early detection before the onset of the disease.