• Na Yin, Pengjie Li, Xuran Li, Xin Li, Yiming Wang, Xiaohan Yu, Yeyun Deng, Chaodong Wang, and Shun Yu.
• Department of Neurobiology and National Clinical Research Center for Geriatrics, Xuanwu Hospital of Capital Medical University, Beijing, China.
• Neuroscience. 2025 Feb 16; 567: 283628-36.

AbstractThe brain of patients with Parkinson's disease (PD) was characterized by increased phosphorylation and oligomerization of α-synuclein (α-syn) and altered activity of enzymes regulating α-syn phosphorylation and oligomerization. Whether increased α-syn phosphorylation and oligomerization as well as related enzyme changes can be detected in the plasma of PD patients remains unclear. Here, we showed that human α-syn proteins incubated in PD plasma formed more oligomerized α-syn (O-α-syn) and phosphorylated α-syn (pS-α-syn) than those in healthy control (HC) plasma. Receiver operating characteristic (ROC) curve indicated that α-syn oligomerization rate and phosphorylation rate discriminated PD patients well from HC subjects. Moreover, they were both positively correlated with Hoehn and Yahr staging and polo-like kinase 2 (PLK2, an enzyme promoting α-syn phosphorylation) levels, and negatively correlated with protein phosphatase 2A levels (PP2A, an enzyme dephosphorylating α-syn) and glucocerebrosidase (GCase, an enzyme whose deficiency causes α-syn oligomerization) activity and ceramide (a product of GCase and a natural PP2A activator) levels. The above results suggest that increased α-syn oligomerization and phosphorylation rates and related enzyme changes can be detected in PD plasma and used to discriminate PD patients from HC subjects and predict PD progression.Copyright © 2025 International Brain Research Organization (IBRO). Published by Elsevier Inc. All rights reserved.

26 keywords...

hide…