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Abstract Details

Toward a Biomarker Panel measured in CNS-originating Extracellular Vesicles for Differential Diagnosis of Parkinson’s Disease and Multiple System Atrophy
Movement Disorders
S37 - Movement Disorders: Phenotyping and Biomarkers (1:48 PM-2:00 PM)
005

EVs contain cell-state specific cargo and cross the blood-brain-barrier into the blood, providing a window into biochemical changes in the CNS. We showed previously that the level of total α-syn was significantly higher in neuronal- and oligodendroglial EVs (nEVs and oEVs, respectively) in the order HC < PD < MSA (Dutta et al. 2021). Separation of MSA from HC or PD was high whereas between PD and HC it was moderate. The level of pS129-α-syn in normal adult brain is ~4% but is substantially higher in PD/MSA brains. Tau aggregates are found in ~50% of PD brains but are rare in MSA.

To test whether pS129-α-synuclein and/or total tau measured in CNS-originating extracellular vesicles (EVs) improve the separation among healthy controls (HC), patients with Parkinson’s disease (PD) and patients with multiple system atrophy (MSA) when combined with total α-synuclein concentrations.

EVs were isolated from serum/plasma by an ExoQuick kit followed by immunoprecipitation of nEVs and oEVs separately. pS129-α-syn (32 HC, 46 PD, 30 MSA) was measured using an in-house developed electrochemilumiscence ELISA (ECLIA). Tau (54 HC, 51 PD, 41 MSA) was measured by a commercial ECLIA kit. Multinomial logistic regression with LASSO variable selection was used for ROC analysis. 

pS129-α-syn was significantly higher in the same order as total α-syn but only in oEVs. Addition of pS129-α-syn in oEVs to the discriminative formula increased the separation among all the groups, particularly between HC and PD. Total tau was significantly lower in nEVs and oEVs in MSA compared to HC and PD though did not increase the separation power.

The accuracy of an algorithm comprising total α-syn in nEVs, oEV:nEV α-syn concentration ratio, pS129-α-syn in oEVs, and total EV concentration is ~80% for discriminating HC from PD, ~99% for separating HC from MSA, and ~93% for distinguishing between PD and MSA.

Authors/Disclosures
Hash Brown Taha
PRESENTER
Mr. Taha has nothing to disclose.
Leony Fenwick, Other Miss Fenwick has nothing to disclose.
Simon Hornung Mr. Hornung has nothing to disclose.
Suman Dutta, PhD (University of California Los Angeles) Dr. Dutta has nothing to disclose.
Kathryn Howe Ms. Howe has nothing to disclose.
Nour Elabed, Other Miss Elabed has nothing to disclose.
Irish Pearl Del Rosario, Other (UCLA) Ms. DEL ROSARIO has nothing to disclose.
Darice Wong Darice Wong has nothing to disclose.
Aline Duarte Folle, PhD (University of California Los Angeles) Dr. Duarte Folle has received research support from Michael J Fox Foundation. Dr. Duarte Folle has received research support from Multiple System Atrophy (MSA) Coalition.
Daniela Markovic, Other (UCLA) Ms. Markovic has nothing to disclose.
Jose-Alberto Palma, MD, PhD, FAAN (New York University Grossman School of Medicine) Dr. Palma has received personal compensation for serving as an employee of Novartis. Dr. Palma has received personal compensation in the range of $10,000-$49,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Clinical Autonomic Research. The institution of Dr. Palma has received research support from National Institutes of Health. Dr. Palma has received publishing royalties from a publication relating to health care.
Un Jung Kang, MD, FAAN (New York University Langone Health) Dr. Kang has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Amprion. Dr. Kang has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for UCB. Dr. Kang 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 Experimental Neurology. The institution of Dr. Kang has received research support from NIH. The institution of Dr. Kang has received research support from Parkinson's Foundation. The institution of Dr. Kang has received research support from Michael J Fox Foundation for Parkinson's Research.
Roy Alcalay, MD (Columbia University) Dr. Alcalay has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Genzyme/Sanofi. Dr. Alcalay has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen. Dr. Alcalay has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Gain Therapeutics. Dr. Alcalay has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Vanqua Bio. Dr. Alcalay has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Takeda. Dr. Alcalay has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biohaven. Dr. Alcalay has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Capsida. Dr. Alcalay has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Servier. The institution of Dr. Alcalay has received research support from Michael J. Fox Foundation. The institution of Dr. Alcalay has received research support from Parkinson's Foundation. The institution of Dr. Alcalay has received research support from Silverstein Foundation. Dr. Alcalay has received personal compensation in the range of $50,000-$99,999 for serving as a Consultant with Parkinson's Foundation.
Miriam M. Sklerov, MD (UNC) The institution of Dr. Sklerov has received research support from National Institutes of Health (NIH). The institution of Dr. Sklerov has received research support from University of North Carolina Department of Medicine.
Horacio C. Kaufmann, MD, FAAN (NYU Langone Health - NYU Dysautonomia Center) Dr. Kaufmann has received personal compensation in the range of $50,000-$99,999 for serving as a Consultant for Theravance. Dr. Kaufmann has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Lilly USA. Dr. Kaufmann has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Takeda Pharmaceuticals. Dr. Kaufmann has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Ono Pharma UK Ltd. Dr. Kaufmann has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Vaxxinity. Dr. Kaufmann 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 Spinger. The institution of Dr. Kaufmann has received research support from Biogen. Dr. Kaufmann has received publishing royalties from a publication relating to health care.
Brent L. Fogel, MD, PhD, FAAN (UCLA Neurology) Dr. Fogel has received personal compensation in the range of $0-$499 for serving as an officer or member of the Board of Directors for National Ataxia Foundation. Dr. Fogel has received personal compensation in the range of $0-$499 for serving as an officer or member of the Board of Directors for Ataxia Global Initiative. Dr. Fogel has received personal compensation in the range of $0-$499 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Neurology Today. Dr. Fogel has received personal compensation in the range of $0-$499 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Neurology Genetics. Dr. Fogel has received personal compensation in the range of $0-$499 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Frontiers in Genetics. Dr. Fogel has received personal compensation in the range of $0-$499 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Genes. The institution of Dr. Fogel has received research support from the National Institutes of Health. The institution of Dr. Fogel has received research support from the National Ataxia Foundation. The institution of an immediate family member of Dr. Fogel has received research support from the National Institutes of Health, the National Science Foundation, and the Department of Defense.
Jeff M. Bronstein, MD, PhD (UCLA) Dr. Bronstein has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Ultragenyx. The institution of Dr. Bronstein has received research support from NIH. The institution of Dr. Bronstein has received research support from Levine Foundation.
Beate Ritz Beate Ritz has received personal compensation in the range of $0-$499 for serving as an officer or member of the Board of Directors for Foundation for Psychocultural Research. Beate Ritz has received personal compensation in the range of $50,000-$99,999 for serving as an Expert Witness for Tillery Korein Law firm. Beate Ritz has received personal compensation in the range of $50,000-$99,999 for serving as an Expert Witness for Andrus Wagstaff law firm. The institution of Beate Ritz has received research support from NIH. The institution of Beate Ritz has received research support from MJFox foundation. The institution of Beate Ritz has received research support from Dept of Defense. The institution of Beate Ritz has received research support from NASA. The institution of Beate Ritz has received research support from MSA foundation.
Gal Bitan, PhD (UCLA) The institution of Dr. Bitan has received research support from NIH/NIA. The institution of Dr. Bitan has received research support from NIH/NINDS. The institution of Dr. Bitan has received research support from The Alzheimer's Association, The Michael J. Fox Foundation, Weston Brain Institute, and Alzheimer's Research UK Biomarkers Across Neurodegenerative Diseases (BAND 3). The institution of Dr. Bitan has received research support from CurePSP. The institution of Dr. Bitan has received research support from The Michael J. Fox Foundation. The institution of Dr. Bitan has received research support from The National Ataxia Foundation. The institution of Dr. Bitan has received research support from Cure Sanfilippo Foundation. Dr. Bitan has received personal compensation in the range of $10,000-$49,999 for serving as a Tutor with Pioneer Academics.