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

Translational Neurodegeneration

Liyan Gao¹  Chen Tian²  Jing Zhang³  Genliang Liu⁴  Tao Feng⁵  Tessandra Stewart⁶  Catherine Pan⁶  Min Shi⁶  David Soltys⁶  Zhiying Xie⁶  Na Liu⁷ 

[1] 0000 0001 0455 0905, grid.410645.2, Department of neurology, Qingdao Municipal Hospital, Qingdao University, Qingdao, China;0000 0004 0369 153X, grid.24696.3f, Center for Neurodegenerative Disease, Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China;0000 0001 2256 9319, grid.11135.37, Department of Pathology, Peking University School of Basic Medical Sciences, Peking University, Beijing, China;0000000122986657, grid.34477.33, Department of Pathology, University of Washington School of Medicine, Seattle, WA, USA;0000 0001 2256 9319, grid.11135.37, Department of Pathology, Peking University School of Basic Medical Sciences, Peking University, Beijing, China;Department of Pathology, Peking University Third Hospital, Peking University, Beijing, China;0000000122986657, grid.34477.33, Department of Pathology, University of Washington School of Medicine, Seattle, WA, USA;Beijing Key Laboratory of Research and Transformation on Neurodegenerative Diseases Biomarkers, Beijing, China;0000 0004 0369 153X, grid.24696.3f, Center for Neurodegenerative Disease, Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China;0000 0004 0642 1244, grid.411617.4, China National Clinical Research Center for Neurological Diseases, Beijing, China;0000 0004 0369 153X, grid.24696.3f, Center for Neurodegenerative Disease, Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China;0000 0004 0642 1244, grid.411617.4, China National Clinical Research Center for Neurological Diseases, Beijing, China;0000 0004 0369 153X, grid.24696.3f, Parkinson’s Disease Center, Beijing Institute for Brain Disorders, Capital Medical University, Beijing, China;0000000122986657, grid.34477.33, Department of Pathology, University of Washington School of Medicine, Seattle, WA, USA;Department of Neurology, Peking University Third Hospital, Peking University, Beijing, China;Beijing Key Laboratory of Research and Transformation on Neurodegenerative Diseases Biomarkers, Beijing, China;

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

DOI  :  10.1186/s40035-019-0155-y

来源: publisher

【 摘 要 】

BackgroundErythrocytes 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.MethodsUsing 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.ResultsThe 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.ConclusionsThese 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】

CC BY