Alpha-synuclein in Blood RBC Extracellular Vesicles is Elevated in Parkinson’s Disease and Correlates with Motor Symptom Severity
Ergun Uc1, Patrick Aro2, Michelle Lenz3, Christina Weber4, Jeffrey Dawson5, Vellareddy Anantharam6, Anumantha Kanthasamy6, Min Shi2
1Neurology, University of Iowa/Iowa City VA Medical Center, 2University of Washington, 3Iowa City VA Medical Center, 4Neurology, 5Biostatistics, University of Iowa, 6University of Georgia-Athens
Objective:
To determine the biomarker potential of alpha-synuclein (aSyn) in red blood cell-derived extracellular vesicles (RBC-EV) in Parkinson’s disease (PD).
Background:
Alpha-synuclein seed amplification assays in cerebrospinal fluid and some biopsy samples have shown promising results in diagnosing synucleinopathies. Simpler and robust markers in easily accessible body fluids (e.g., blood) are still urgently needed to aid in PD diagnosis. RBCs and their EVs are one of the major sources of aSyn in blood but its diagnostic potential in PD has yet to be determined.
Design/Methods:
Forty-two PD patients and 33 Controls with non-PD/non-neurodegenerative neurological conditions from the Neurology Outpatient Clinic at a Veterans Affairs Hospital underwent MDS-UPDRS and MoCA testing in a cross-sectional study. Blood samples were processed to culture RBCs, isolate and quantify EVs, and measure the aSyn concentrations in RBC-EVs by ELISA.
Results:
The PD group (median Hoehn-Yahr stage II, range I-V) was older (median age 75 vs. 71, p<0.01) and scored significantly higher on MDS-UPDRS after adjusting for age: p<0.001 for MDS2 (motor experiences of daily living), MDS3 (motor examination], MDS123 (total); p<0.01 for non-motor EDL subscale MDS1_Autonomic and p<0.05 for MDS1_Complex Behavioral. There was no group difference in MoCA (median 24/30 in both groups). The aSyn concentrations in RBC-EVs were higher in PD vs. Controls: median levels 19,590 vs. 7,109 pg/AU; p=0.022, adjusted for age. Within the PD group, there were significant positive correlations between RBC-EV aSyn concentrations and MDS-UPDRS scores after adjusting for age: MDS2 rho=0.41, p<0.01; MDS3 rho=0.32, p<0.05; MDS123 rho=0.35, p<0.05.
Conclusions:
Our preliminary results suggest that the aSyn concentrations in blood RBC-EVs can differentiate between PD and Control groups, and correlate with motor symptom severity in PD. Further research is warranted to determine if RBC-EV aSyn concentrations and its seeding activity can be used as a convenient and feasible diagnostic test and biomarker of PD severity.
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