Abstract Details

Title Alpha-synuclein in Blood RBC Extracellular Vesicles is Elevated in Parkinson’s Disease and Correlates with Motor Symptom Severity

Topic Movement Disorders

Presentation(s) S4 - Movement Disorders: Basic Science (1:24 PM-1:36 PM)

Poster/Presentation
Number 003

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.

Objective To determine the biomarker potential of alpha-synuclein (aSyn) in red blood cell-derived extracellular vesicles (RBC-EV) in Parkinson’s disease (PD).

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.

Authors/Disclosures
Ergun Y. Uc, MD (University of Iowa) PRESENTER	An immediate family member of Dr. Uc has received personal compensation in the range of $500-$4,999 for serving as an officer or member of the Board of Directors for American Board of Pediatrics. The institution of Dr. Uc has received research support from Department of Veterans Affairs. The institution of Dr. Uc has received research support from Department of Defense. The institution of an immediate family member of Dr. Uc has received research support from NIH. The institution of Dr. Uc has received research support from NIH. The institution of Dr. Uc has received research support from NIH. The institution of Dr. Uc has received research support from Parkinson's Foundation. The institution of Dr. Uc has received research support from NIH.
Patrick Aro, MS	Mr. Aro has nothing to disclose.
Michelle E. Lenz, RN	Ms. Lenz has received personal compensation for serving as an employee of VA Research Foundation.
Christina Weber (University of Iowa Hospitals and Clinics)	Christina Weber has nothing to disclose.
Jeffrey Dawson	Jeffrey Dawson has received personal compensation in the range of $500-$4,999 for serving as a Consultant for iotaMotion. Jeffrey Dawson has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Congress of Neurological Surgeons. The institution of Jeffrey Dawson has received research support from Department of Veterans Affairs. The institution of Jeffrey Dawson has received research support from NIH.
Vellareddy Anantharam, PhD	Dr. Anantharam has nothing to disclose.
Anumantha G. Kanthasamy (Parkinson's & Movement Disorders Inst)	Anumantha G. Kanthasamy has received personal compensation for serving as an employee of Probiome Therapeutics. Anumantha G. Kanthasamy has received personal compensation in the range of $500-$4,999 for serving as a Consultant for National Institute of Health. Anumantha G. Kanthasamy has stock in Google, meta and Amazon. The institution of Anumantha G. Kanthasamy has received research support from NIH , DoD and MJFF. Anumantha G. Kanthasamy has received intellectual property interests from a discovery or technology relating to health care. Anumantha G. Kanthasamy has received personal compensation in the range of $500-$4,999 for serving as a Consultant with NIH.
Min Shi, PhD	The institution of Dr. Shi has received research support from NIH. The institution of Dr. Shi has received research support from DoD.

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