Erythrocytic α-Synuclein as a potential biomarker for Parkinson’s disease

Translational Neurodegeneration

Na Liu¹  Genliang Liu²  Tao Feng²  Liyan Gao²  Chen Tian³  Jing Zhang³  Catherine Pan⁴  Tessandra Stewart⁴  David Soltys⁴  Zhiying Xie⁴  Min Shi⁴ 

[1] Beijing Key Laboratory of Research and Transformation on Neurodegenerative Diseases Biomarkers;Center for Neurodegenerative Disease, Department of Neurology, Beijing Tiantan Hospital, Capital Medical University;Department of Pathology, Peking University School of Basic Medical Sciences, Peking University;Department of Pathology, University of Washington School of Medicine;

关键词: Parkinson’s disease;    α-Synuclein;    Erythrocyte;    Electrochemiluminescence;   

DOI  :  10.1186/s40035-019-0155-y

来源: DOAJ

【 摘 要 】

Abstract Background Erythrocytes are a major source of peripheral α-synuclein (α-Syn). The goal of the current investigation is to evaluate erythrocytic total, oligomeric/aggregated, and phosphorylated α-Syn species as biomarkers of Parkinson’s disease (PD). PD and healthy control blood samples were collected along with extensive clinical history to determine whether total, phosphorylated, or aggregated α-Syn derived from erythrocytes (the major source of blood α-Syn) are more promising and consistent biomarkers for PD than are free α-Syn species in serum or plasma. Methods Using newly developed electrochemiluminescence assays, concentrations of erythrocytic total, aggregated and phosphorylated at Ser129 (pS129) α-Syn, separated into membrane and cytosolic components, were measured in 225 PD patients and 133 healthy controls and analyzed with extensive clinical measures. Results The total and aggregated α-Syn levels were significantly higher in the membrane fraction of PD patients compared to healthy controls, but without alterations in the cytosolic component. The pS129 level was remarkably higher in PD subjects than in controls in the cytosolic fraction, and to a lesser extent, higher in the membrane fraction. Combining age, erythrocytic membrane aggregated α-Syn, and cytosolic pS129 levels, a model generated by using logistic regression analysis was able to discriminate patients with PD from neurologically normal controls, with a sensitivity and a specificity of 72 and 68%, respectively. Conclusions These results suggest that total, aggregated and phosphorylated α-Syn levels are altered in PD erythrocytes and peripheral erythrocytic α-Syn is a potential PD biomarker that needs further validation.

【 授权许可】

Unknown