Abstract Details

Title Poly (ADP-Ribose) and a–synuclein extracellular vesicles in patients with Parkinson disease: A possible biomarker of disease severity

Topic Movement Disorders

Presentation(s) P14 - Poster Session 14 (11:45 AM-12:45 PM)

Poster/Presentation
Number 5-002

Objective No surrogate biomarkers of Parkinson disease (PD) have been identified. On the other hand, a non-invasive biomarker is crucial to understand the natural history, severity, and progression of Parkinson disease and to guide future therapeutic trials. This exploratory study evaluated the role of extracellular vesicles (EVs) and poly ADP-ribose polymerase (PAR) in plasma of Parkinson disease patients as a non-invasive marker of disease severity and progression.

Background NA

Design/Methods We collected plasma of 57 Parkinson disease patients (discovery cohort 20, replication cohort 37) and compared with 20 unaffected individuals, 20 cases of clinically diagnosed Alzheimer’s disease, and dementia with Lewy bodies. We analyzed alpha-synuclein-positive EVs from platelet-free plasma by nanoscale flow cytometry and blood concentrations of PAR using sandwich ELISA kits.

Results Median concentration of α-synuclein EVs was significantly higher in PD patients compared to the other groups (Kruskal-Wallis, p < .0001). In the discovery cohort, patients with higher α-synuclein extracellular vesicles had a higher Unified Parkinson Disease Rating Scale score (UPDRS III median =22 vs. 5, p=0.045). Seven out of 20 patients (35%) showed detectable PAR levels with positive patients showing significantly higher levels of α-synuclein EVs. In the confirmatory cohort, we did not observe a significant difference in the PAR positive cases in relationship with UPDRS.

Conclusions Non-invasive determination of α-synuclein-positive EVs may provide a potential non-invasive marker of PD disease severity and longitudinal studies are needed to evaluate the role of α-synuclein-positive EVs as marker of disease progression.

Authors/Disclosures
PRESENTER	No disclosure on file
Eduardo E. Benarroch, MD, FAAN (Mayo Clinic)	Dr. Benarroch has nothing to disclose.
Aidan Mullan (Mayo Clinic)	Aidan Mullan has nothing to disclose.
Farwa Ali, MD (Mayo Clinic)	Dr. Ali has nothing to disclose.
Bradley F. Boeve, MD, FAAN (Mayo Clinic)	Dr. Boeve has received personal compensation in the range of $10,000-$49,999 for serving as an officer or member of the Board of Directors for Rainwater Charitable Foundation. The institution of Dr. Boeve has received research support from Alector. The institution of Dr. Boeve has received research support from EIP Pharma. The institution of Dr. Boeve has received research support from Transposon. The institution of Dr. Boeve has received research support from Cognition Therapeutics. Dr. Boeve has received publishing royalties from a publication relating to health care.
Michelle M. Mielke, PhD (Wake Forest University School of Medicine)	Dr. Mielke has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Merck. Dr. Mielke has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Eisai. Dr. Mielke has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Eli Lilly. Dr. Mielke has received personal compensation in the range of $500-$4,999 for serving as a Consultant for LabCorp. Dr. Mielke has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Roche. Dr. Mielke has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Siemens Healthineers. Dr. Mielke has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sunbird Bio. Dr. Mielke has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Eisai. Dr. Mielke has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Roche. Dr. Mielke has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Novo Nordisk.
Ronald C. Petersen, MD, PhD, FAAN (Mayo Clinic)	Dr. Petersen has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche. Dr. Petersen has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Genentech. Dr. Petersen has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Eli Lilly and Co.. Dr. Petersen has received personal compensation in the range of $0-$499 for serving as a Consultant for Eisai, Inc.. Dr. Petersen has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novo Nordisk. Dr. Petersen has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis. Dr. Petersen has received publishing royalties from a publication relating to health care. Dr. Petersen has received publishing royalties from a publication relating to health care. Dr. Petersen has received publishing royalties from a publication relating to health care. Dr. Petersen has a non-compensated relationship as a Board of Directors with American Brain Foundation that is relevant to AAN interests or activities.
Cole D. Stang	Mr. Stang has nothing to disclose.
Emanuele Camerucci, MD (Kansas University Medical Center)	Dr. Camerucci has nothing to disclose.
Owen A. Ross, PhD (Mayo Clinic Jacksonville)	Dr. Ross has nothing to disclose.
Zbigniew K. Wszolek, MD, FAAN (Mayo Clinic- Jacksonville)	Dr. Wszolek has received personal compensation in the range of $5,000-$9,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Polish Neurological Society/Via Medica. Dr. Wszolek has received intellectual property interests from a discovery or technology relating to health care.
David S. Knopman, MD, FAAN (Mayo Clinic)	Dr. Knopman has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for DIAN TU study. The institution of Dr. Knopman has received research support from NIH.
James H. Bower, MD, MSc, FAAN (Mayo Clinic)	The institution of Dr. Bower has received research support from Abbvie.
Wolfgang Singer, MD, FAAN (Mayo Clinic)	Dr. Singer has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biohaven. The institution of Dr. Singer has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Lundbeck. Dr. Singer has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Ionis. Dr. Singer has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Yoda. Dr. Singer has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Theravance. Dr. Singer has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Ferrer. The institution of Dr. Singer has received research support from NIH. The institution of Dr. Singer has received research support from FDA. The institution of Dr. Singer has received research support from Michael J. Fox Foundation. Dr. Singer has received intellectual property interests from a discovery or technology relating to health care.
Rodolfo Savica, MD, PhD, FAAN (Mayo Clinic)	The institution of Dr. Savica has received research support from ACADIA Pharmaceuticals, Inc.

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