Erythrocytic α-Synuclein in Parkinson’s Disease and Progressive Supranuclear Palsy—A Pilot Study

<b>Background/Objectives:</b> The current research examines the accuracy of α-synuclein in RBCs as a diagnostic biomarker for PD and PSP, despite their distinct molecular etiologies. <b>Methods:</b> We used ELISA to measure total, oligomeric, and p129-α-synuclein levels in erythrocytes from 8 PSP patients, 19 PD patients, and 18 healthy controls (HCs). The classification performances of RBC α-synuclein levels were investigated by receiver operator characteristic (ROC) curve. We also evaluated a possible correlation between RBC α-synuclein level and the biological and clinical features of our cohorts. <b>Results:</b> RBC total α-synuclein was higher in PSP patients compared to both PD patients and HCs, achieving good classification performance (AUC: 0.853) in distinguishing PSP patients from PD patients, with a sensitivity of 100% and a specificity of 70.6%; moreover, the levels of this biomarker positively correlated with disease severity in PSP group. Regarding oligomeric α-synuclein and p129-α-synuclein, the latter was slightly increased in RBCs from PSP patients compared to HCs, but no correlations were detected. <b>Conclusions:</b> Although these findings need to be confirmed in larger studies, our pilot work suggests that RBC total α-synuclein may represent a potential molecular biomarker for the differential diagnosis and clinical staging of PSP.