TY - JOUR
T1 - Complement system changes in blood in Parkinson's disease and progressive Supranuclear Palsy/Corticobasal Syndrome
AU - Khosousi, Shervin
AU - Hye, Abdul
AU - Velayudhan, Latha
AU - Bloth, Björn
AU - Tsitsi, Panagiota
AU - Markaki, Ioanna
AU - Svenningsson, Per
N1 - Funding Information:
We would like to thank all the study participants in the BIOPARK and AETIONOMY cohorts for donating blood samples. We also thank all the clinicians who took part in assessing and recruiting patients, collecting biological samples, and coordinating cohort logistics. The authors would also like to thank the members of the AETIONOMY Clinical Consortium, particularly at the Stockholm site. Finally, we want to thank CBD solutions and Van Geest Foundation for funding the project.
Publisher Copyright:
© 2023
PY - 2023/3
Y1 - 2023/3
N2 - 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.
AB - 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.
KW - Atypical parkinsonism
KW - Biomarkers
KW - Complement factors
KW - Parkinson's disease
KW - Plasma
KW - Tauopathies
UR - http://www.scopus.com/inward/record.url?scp=85147803442&partnerID=8YFLogxK
U2 - 10.1016/j.parkreldis.2023.105313
DO - 10.1016/j.parkreldis.2023.105313
M3 - Article
C2 - 36739794
AN - SCOPUS:85147803442
SN - 1353-8020
VL - 108
JO - Parkinsonism and Related Disorders
JF - Parkinsonism and Related Disorders
M1 - 105313
ER -