Interdisciplinary Neuroscience Research Program (INRP), Tehran University of Medical Sciences, Tehran, Iran.
Multiple Sclerosis Research Center (MSRC), Sina Hospital, Tehran University of Medical Sciences, Tehran, Iran.
Mov Disord. 2018 Mar;33(3):431-439. doi: 10.1002/mds.27284. Epub 2018 Feb 13.
Pathological accumulation of α-synuclein, amyloid-β , and tau proteins in the brain is considered critical for development of various neurodegenerative diseases.
We investigated the association between CSF levels of these biomarkers, brain structural connectivity, and the UPDRS in PD.
Diffusion tensor images and CSF biomarkers (α-synuclein, amyloid-β , total tau, and phosphorylated tau181) from 132 drug-naïve, nondemented PD patients and 61 healthy controls were obtained from the Parkinson's Progression Markers Initiative database. After network reconstruction of structural connectivity patterns, global interconnectivity measures (including global efficiency, clustering coefficient, and characteristic path length) and local efficiency were calculated. Network properties and CSF biomarkers were compared between PD patients and healthy controls. The association of CSF biomarkers with network properties and UPDRS-III score was investigated.
Global measures (but not local efficiency) and CSF α-synuclein were significantly lower in PD patients. Global efficiency and clustering coefficient correlated positively with α-synuclein, Aβ , and total tau CSF levels. Furthermore, these CSF biomarkers showed no significant association with the UPDRS-III score.
This study examined the association of CSF biomarkers that reflect the brain pathology, with structural brain connectivity and UPDRS-III in PD. Our results revealed an association between the abnormal aggregation of α-synuclein, Aβ , and tau proteins and structural connectivity disruption in PD patients. In summary, a combination of structural imaging and measurement of CSF biomarkers provide a better understanding of the pathogenesis of PD. © 2018 International Parkinson and Movement Disorder Society.
脑内α-突触核蛋白、淀粉样β和tau 蛋白的病理性积累被认为是各种神经退行性疾病发展的关键。
我们研究了这些生物标志物的 CSF 水平与 PD 患者的脑结构连接和 UPDRS 之间的关系。
从帕金森进展标志物倡议数据库中获得了 132 名未经药物治疗的非痴呆 PD 患者和 61 名健康对照者的弥散张量图像和 CSF 生物标志物（α-突触核蛋白、淀粉样β、总 tau 和磷酸化 tau181）。在结构连接模式的网络重建后，计算了全局连通性度量（包括全局效率、聚类系数和特征路径长度）和局部效率。比较了 PD 患者和健康对照组之间的网络特性和 CSF 生物标志物。研究了 CSF 生物标志物与网络特性和 UPDRS-III 评分的关系。
PD 患者的全局度量（而非局部效率）和 CSF α-突触核蛋白明显降低。全局效率和聚类系数与 CSF α-突触核蛋白、Aβ和总 tau 呈正相关。此外，这些 CSF 生物标志物与 UPDRS-III 评分无显著相关性。
本研究探讨了反映脑病理学的 CSF 生物标志物与 PD 患者的脑结构连接和 UPDRS-III 的关系。我们的研究结果揭示了 PD 患者中 α-突触核蛋白、Aβ和 tau 蛋白异常聚集与结构连接中断之间存在关联。总之，结构成像与 CSF 生物标志物的测量相结合，为 PD 的发病机制提供了更好的理解。
