Abstract Details

Title Alpha-Synuclein Oligomers and Neurofilament Light Chain Predict Phenoconversion of Pure Autonomic Failure

Topic Autonomic Disorders

Presentation(s) S30 - Autonomic Disorders (3:42 PM-3:54 PM)

Poster/Presentation
Number 002

Background Even though certain clinical characteristics can help in the prediction of future phenoconversion of patients with PAF to MSA, clinical predictors remain imperfect. ASyn oligomers and NfL have recently emerged as powerful biomarkers differentiating early MSA from Lewy body synucleinopathies.

Objective To explore the role of alpha-synuclein (αSyn) oligomers and neurofilament light chain (NfL) in cerebrospinal fluid (CSF) of patients with pure autonomic failure (PAF) as markers of future phenoconversion to multiple system atrophy (MSA).

Design/Methods

Well-characterized patients with PAF (n=32) were enrolled between June 2016 and February 2019 at Mayo Clinic Rochester and followed prospectively with annual visits to determine future phenoconversion to MSA, Parkinson’s disease (PD), or dementia with Lewy bodies (DLB). ELISA was utilized to measure NfL and protein misfolding cyclic amplification (PMCA) to detect αSyn oligomers in CSF collected at baseline.

Results Patients were followed for a median of 3.9 years. 5 patients converted to MSA, 2 to PD, and 2 to DLB. NfL at baseline was elevated only in patients who later developed MSA, perfectly separating those from future PD and DLB converters as well as non-converters. ASyn-PMCA was positive in all but 2 cases (94%). The PMCA reaction was markedly different in 5 samples with maximum fluorescence and reaction kinetics previously described in MSA patients; all of these patients later developed MSA.

Conclusions

αSyn-PMCA is almost invariably positive in the CSF of patients with PAF establishing this condition as α-synucleinopathy. Both NfL and the magnitude and reaction kinetics of αSyn PMCA faithfully predict which PAF patients will eventually phenoconvert to MSA. This finding has important implications not only for prognostication, but also for future trials of disease modifying therapies, allowing for differentiation of MSA from Lewy body synucleinopathies before motor symptoms develop.

Authors/Disclosures
Wolfgang Singer, MD (Mayo Clinic) PRESENTER	Dr. Singer has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Amneal. Dr. Singer has received personal compensation in the range of $500-$4,999 for serving as a Consultant for UniQure. Dr. Singer has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biohaven. Dr. Singer has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Theravance. 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.
Ann M. Schmeichel	Ann M. Schmeichel has nothing to disclose.
Mohammad Shahnawaz, PhD (University of Texas Health Science Center At Houston)	The institution of Dr. Shahnawaz has received research support from American Parkinson Disease Association. The institution of Dr. Shahnawaz has received research support from NIH. The institution of Dr. Shahnawaz has received research support from Texas Alzheimer's Research & Care Consortium . Dr. Shahnawaz has received intellectual property interests from a discovery or technology relating to health care.
	No disclosure on file
David M. Sletten, MBA (Mayo Clinic)	Mr. Sletten has nothing to disclose.
Tonette Gehrking	Tonette Gehrking has nothing to disclose.
Jade Gehrking (Mayo Clinic, Neurology Dept)	Jade Gehrking has nothing to disclose.
Mariana Suarez	No disclosure on file
	No disclosure on file
Claudio Soto (University of Texas Medical Branch)	Claudio Soto has received personal compensation in the range of $50,000-$99,999 for serving as a Consultant for Amprion. Claudio Soto has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Rinri therapeutics. Claudio Soto has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Affyxell Therapeutics. Claudio Soto has stock in Amprion. The institution of Claudio Soto has received research support from NIH. The institution of Claudio Soto has received research support from Michael J. Fox Foundation. The institution of an immediate family member of Claudio Soto has received research support from NIH. Claudio Soto has received intellectual property interests from a discovery or technology relating to health care.
Phillip A. Low, MD, FAAN (Mayo Clinic)	Dr. Low has nothing to disclose.