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.

中文翻译：

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早期阿尔茨海默病的 Tau 病理学与神经生理网络动力学的选择性破坏有关

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症至关重要。我们测试了 Tau 病理学与广泛的神经生理网络的功能组织相关的假设。我们使用带有 [18F]AV-1451 PET 扫描的脑磁图来量化依赖于 Tau 的网络变化。我们使用大脑连接的图论方法，量化了功能隔离、中心性和信息传输效率的节点测量，并根据 [18F]AV-1451 的水平对其进行了测试。早期阿尔茨海默氏病中较高的 Tau 负荷与最佳小世界组织的转变以及 β 和 γ 带中更加分散的网络有关，由此顶枕区与网络的前部断开。同样，更高的 Tau 负荷与局部和全局效率的降低有关，尤其是在伽马波段。该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。