Research Imaging Centre, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, University of Toronto, Toronto, Ontario, Canada.
Division of Brain, Imaging and Behaviour - Systems Neuroscience, Krembil Research Institute, University Health Network, University of Toronto, Toronto, Ontario, Canada.
Mol Neurobiol. 2019 Nov;56(11):7731-7740. doi: 10.1007/s12035-019-1625-z. Epub 2019 May 20.
Beta-amyloid (Aβ) in the brain is a key pathological feature of certain neurodegenerative diseases. Recent studies using graph theory have shown that Aβ brain networks are of pathological significance in Alzheimer's disease (AD). However, the characteristics of Aβ brain networks in Parkinson's disease (PD) are unknown. In the present study using positron emission tomography (PET) with [C]-Pittsburgh compound B (PiB), we applied a graph theory-based analysis to assess the topological properties of Aβ brain network in PD patients with and without Aβ burden (PiB-positive and PiB-negative, respectively) and healthy controls with Aβ burden. We found that the PD PiB-positive group demonstrated significantly lower value in global efficiency and modularity compared with PD PiB-negative group. The less robust modular structure indicates the tendency of having increased inter-modular connections than intra-modular connectivity (i.e., reduced segregation). Results of hub organization showed that relative to PD PiB-negative group, different hubs were identified in the PiB-positive group, which were located mainly within the default mode network. Overall, our findings suggest disturbances in Aβ topological organization characterized by abnormal network integration and segregation in PD patients with Aβ burden. The stronger inter-modular connectivity observed in the PD PiB-positive group may suggest the spreading pattern of Aβ between modules in those PD patients with elevated PiB burden, thus providing insight into the beta-amyloidopathy of PD.
脑内的β-淀粉样蛋白（Aβ）是某些神经退行性疾病的关键病理特征。最近使用图论的研究表明，Aβ脑网络在阿尔茨海默病（AD）中具有病理意义。然而，帕金森病（PD）中 Aβ脑网络的特征尚不清楚。在本研究中，我们使用正电子发射断层扫描（PET）与 [C]-匹兹堡化合物 B（PiB），应用基于图论的分析方法评估了有和无 Aβ负担（分别为 PiB 阳性和 PiB 阴性）的 PD 患者以及有 Aβ负担的健康对照者的 Aβ脑网络的拓扑性质。我们发现，与 PD PiB 阴性组相比，PD PiB 阳性组的全局效率和模块度值显著降低。模块化结构较弱表明，与模块内连接相比，模块间连接的趋势增加（即，分离减少）。枢纽组织的结果表明，与 PD PiB 阴性组相比，PiB 阳性组中确定了不同的枢纽，这些枢纽主要位于默认模式网络内。总的来说，我们的研究结果表明，在有 Aβ负担的 PD 患者中，Aβ拓扑组织存在紊乱，表现为网络整合和分离异常。在 PD PiB 阳性组中观察到的更强的模块间连接可能提示在那些 Aβ负担升高的 PD 患者中 Aβ在模块之间的扩散模式，从而深入了解 PD 的β-淀粉样蛋白病。
