Kesler Shelli R, Acton Paul, Rao Vikram, Ray William J
Department of Neuro-oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Neurodegeneration Consortium, Institute for Applied Cancer Science, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Netw Neurosci. 2018 Jun 1;2(2):241-258. doi: 10.1162/netn_a_00048. eCollection 2018.
Neurodegeneration in Alzheimer's disease (AD) is associated with amyloid-beta peptide accumulation into insoluble amyloid plaques. The five-familial AD (5XFAD) transgenic mouse model exhibits accelerated amyloid-beta deposition, neuronal dysfunction, and cognitive impairment. We aimed to determine whether connectome properties of these mice parallel those observed in patients with AD. We obtained diffusion tensor imaging and resting-state functional magnetic resonance imaging data for four transgenic and four nontransgenic male mice. We constructed both structural and functional connectomes and measured their topological properties by applying graph theoretical analysis. We compared connectome properties between groups using both binarized and weighted networks. Transgenic mice showed higher characteristic path length in weighted structural connectomes and functional connectomes at minimum density. Normalized clustering and modularity were lower in transgenic mice across the upper densities of the structural connectome. Transgenic mice also showed lower small-worldness index in higher structural connectome densities and in weighted structural networks. Hyper-correlation of structural and functional connectivity was observed in transgenic mice compared with nontransgenic controls. These preliminary findings suggest that 5XFAD mouse connectomes may provide useful models for investigating the molecular mechanisms of AD pathogenesis and testing the effectiveness of potential treatments.
阿尔茨海默病（AD）中的神经退行性变与β淀粉样肽聚积形成不溶性淀粉样斑块有关。五家族性AD（5XFAD）转基因小鼠模型表现出加速的β淀粉样蛋白沉积、神经元功能障碍和认知障碍。我们旨在确定这些小鼠的连接组特性是否与AD患者中观察到的特性相似。我们获取了4只转基因雄性小鼠和4只非转基因雄性小鼠的扩散张量成像和静息态功能磁共振成像数据。我们构建了结构连接组和功能连接组，并通过应用图论分析测量它们的拓扑特性。我们使用二值化网络和加权网络比较了两组之间的连接组特性。转基因小鼠在加权结构连接组和最低密度的功能连接组中表现出更高的特征路径长度。在结构连接组的较高密度下，转基因小鼠的标准化聚类和模块化程度较低。转基因小鼠在较高的结构连接组密度和加权结构网络中也表现出较低的小世界指数。与非转基因对照相比，在转基因小鼠中观察到结构和功能连接的超相关性。这些初步发现表明，5XFAD小鼠连接组可能为研究AD发病机制的分子机制和测试潜在治疗方法的有效性提供有用的模型。
