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

Background: Erythrocytes are a major source of peripheral alpha-synuclein (alpha-Syn). The goal of the current investigation is to evaluate erythrocytic total, oligomeric/aggregated, and phosphorylated alpha-Syn species as biomarkers of Parkinson's disease (PD). PD and healthy control blood samples were collected along with extensive clinical historyto determine whether total, phosphorylated, or aggregated alpha-Syn derived from erythrocytes (the major source of blood alpha-Syn) are more promising and consistent biomarkers for PD than are free alpha-Syn species in serum or plasma. Methods: Using newly developed electrochemiluminescence assays, concentrations of erythrocytic total, aggregated and phosphorylated at Ser129 (pS129) alpha-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 alpha-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 alpha-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 alpha-Syn levels are altered in PD erythrocytes and peripheral erythrocytic alpha-Syn is a potential PD biomarker that needs further validation.