Tau pathology in early Alzheimer's disease is linked to selective disruptions in neurophysiological network dynamics
Tau pathology in early Alzheimer's disease is linked to selective disruptions in neurophysiological network dynamics
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DOI：
10.1016/j.neurobiolaging.2020.03.009
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发表时间：
2020-08-01
影响因子：
4.2
通讯作者：
Rowe, James B.
中科院分区：
文献类型：
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作者：
Kocagoncu, Ece;Quinn, Andrew;Rowe, James B.
了解Tau蛋白聚集在阿尔茨海默病发病机制中的作用对于开发新的基于Tau的治疗策略以减缓或预防痴呆至关重要。我们测试了Tau病理与广泛的神经生理网络的功能组织相关的假设。我们使用脑电磁图和[18F]AV-1451 PET扫描来量化Tau依赖性网络变化。使用大脑连接的图论方法，我们量化了功能分离，中心性和信息传递效率的节点测量，并针对[18 F]AV-1451水平进行了测试。早期阿尔茨海默病中较高的Tau负担与远离最佳小世界组织的转变以及β和γ波段中更碎片化的网络相关，其中顶枕区与网络的前部断开连接。同样，较高的Tau负担与局部和全局效率的降低有关，尤其是在γ波段。这些结果支持阿尔茨海默病神经生理学“特征”的转化发展，以了解人类的疾病机制并促进实验医学研究。
Understanding the role of Tau protein aggregation in the pathogenesis of Alzheimer's disease is critical for the development of new Tau-based therapeutic strategies to slow or prevent dementia. We tested the hypothesis that Tau pathology is associated with functional organization of widespread neurophysiological networks. We used electro-magnetoencephalography with [18F]AV-1451 PET scanning to quantify Tau-dependent network changes. Using a graph theoretical approach to brain connectivity, we quantified nodal measures of functional segregation, centrality, and the efficiency of information transfer and tested them against levels of [18F]AV-1451. Higher Tau burden in early Alzheimer's disease was associated with a shift away from the optimal small-world organization and a more fragmented network in the beta and gamma bands, whereby parieto-occipital areas were disconnected from the anterior parts of the network. Similarly, higher Tau burden was associated with decreases in both local and global efficiency, especially in the gamma band. The results support the translational development of neurophysiological “signatures” of Alzheimer's disease, to understand disease mechanisms in humans and facilitate experimental medicine studies.