ABSTRACT

Background: Pathological accumulation of α-synuclein, amyloid-β42, and tau proteins in the brain is considered critical for development of various neurodegenerative diseases.

Objectives: We investigated the association between CSF levels of these biomarkers, brain structural connectivity, and the UPDRS in PD.

Methods: Diffusion tensor images and CSF biomarkers (α-synuclein, amyloid-β42, 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.

Results: 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, Aβ42, and total tau CSF levels. Furthermore, these CSF biomarkers showed no significant association with the UPDRS-III score.

Conclusions: 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, Aβ42, 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

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