Complement system changes in blood in Parkinson's disease and progressive Supranuclear Palsy/Corticobasal Syndrome

Parkinson's Disease (PD) is diagnosed clinically, and early PD is often challenging to differentiate from atypical parkinsonian disorders such as the Four-repeat (4R-) Tauopathies Progressive Supranuclear Palsy and Corticobasal Syndrome. Diagnostic biomarkers are needed, and proteomic studies have suggested that the plasma complement system is altered in PD, but validation studies are lacking. In this study, plasma from 148 individuals (PD, 4R-Tauopathies, and healthy controls (HC)) were used to quantify 12 complement proteins with immunoassays, and CH50 classical pathway complement activity was quantified in sera from further 78 individuals (PD and HC). Complement factors C1q and C3 in plasma were lower in individuals with 4R-Tauopathies (ANOVA, p = 0.0041, p = 0.0057 respectively) compared to both PD and HC. None of the complement proteins were altered between PD and HC, however a few proteins correlated with clinical parameters within the PD group. Notably, levels of C3 correlated with non-motor symptoms in female patients. Classical pathway complement activity was not altered in PD serum, but did correlate with mental fatigue. In conclusion, individuals with 4R-Tauopathies showed lower plasma C1q and C3 compared PD and HC. Neither complement levels nor CH50 activity were significantly altered in PD versus HC but may associate with PD symptom severity.