Characterizing Network Selectiveness to the Dynamic Spreading of Neuropathological Events in Alzheimer's Disease.
Characterizing Network Selectiveness to the Dynamic Spreading of Neuropathological Events in Alzheimer's Disease.
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DOI：
10.3233/jad-215596
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发表时间：
2022
影响因子：
4
通讯作者：
Wu, Guorong
中科院分区：
文献类型：
--
作者：
Li, Wenchao;Yang, Defu;Yan, Chenggang;Chen, Minghan;Li, Quefeng;Zhu, Wentao;Wu, Guorong
越来越多的证据表明，在阿尔茨海默病(AD)的动态发展过程中，神经病理负担明显偏向于影响大脑的区域。由于不同的大脑区域是由白质纤维物理连接的，因此可以合理地假设神经病理负担的不同传播模式可能是连接拓扑的基础，这可以利用神经成像和网络科学技术来表征。研究阿尔茨海默病(AD)神经病理事件的动态传播规律。我们首先检查大脑网络中具有高连接性的中枢节点(白质连接的集合)是否比网络中参与信息交换过程的其他区域更容易受到更高水平的病理负担的影响。此外，我们提出了一个新的线性混合效应模型来描述神经病理负担从中枢节点到非中枢节点的多因素扩散过程，其中年龄、性别和APOE4指标被视为混杂因素。我们将我们的统计模型分别应用于淀粉样蛋白-PET和tau-PET的纵向神经成像数据。我们的元数据分析结果表明，1)AD对中枢节点的影响不同，其病理水平明显更高；2)非中枢节点上神经病理负担的纵向增加与连接到中枢节点的距离密切相关，而不是空间上的接近程度。阿尔茨海默病的神经病理负担的传播途径可能始于中枢区域，并通过白质纤维以普恩样蛋白的方式传播。
Mounting evidence shows that the neuropathological burdens manifest preference in affecting brain regions during the dynamic progression of Alzheimer’s disease (AD). Since the distinct brain regions are physically wired by white matter fibers, it is reasonable to hypothesize the differential spreading pattern of neuropathological burdens may underlie the wiring topology, which can be characterized using neuroimaging and network science technologies. To study the dynamic spreading patterns of neuropathological events in AD. We first examine whether hub nodes with high connectivity in the brain network (assemble of white matter wirings) are susceptible to a higher level of pathological burdens than other regions that are less involved in the process of information exchange in the network. Moreover, we propose a novel linear mixed-effect model to characterize the multi-factorial spreading process of neuropathological burdens from hub nodes to non-hub nodes, where age, sex, and APOE4 indicators are considered as confounders. We apply our statistical model to the longitudinal neuroimaging data of amyloid-PET and tau-PET, respectively. Our meta-data analysis results show that 1) AD differentially affects hub nodes with a significantly higher level of pathology, and 2) the longitudinal increase of neuropathological burdens on non-hub nodes is strongly correlated with the connectome distance to hub nodes rather than the spatial proximity. The spreading pathway of AD neuropathological burdens might start from hub regions and propagate through the white matter fibers in a prion-like manner.