Abstract Details

Title A rapid, ultra-sensitive, RT-QuIC assay, with novel protocol, for MSA and PD using a single site skin biopsy and serum neurofilament light chain.

Topic Movement Disorders

Presentation(s) P1 - Poster Session 1 (9:00 AM-5:00 PM)

Poster/Presentation
Number 235

Objective

To reliably and rapidly distinguish multiple system atrophy (MSA) from Parkinson’s disease (PD), Progressive Supranuclear Palsy (PSP), and healthy controls (HC) using a minimally invasive skin biopsy, a novel Real-Time Quaking-induced Conversion (RT-QuIC) protocol for alpha-synuclein (aSyn) detection, and serum neurofilament light chain (NfL).

Background

Clinical features of PD/MSA/PSP frequently overlap; diagnosis, is often challenging. RT-QuIC has been adapted to detect aSyn in CSF where it differentiates PD from HC with >90% sensitivity/specificity.

Design/Methods

One RT-QuIC study reported a sensitivity of 95.4% (specificity 93%) in MSA after 12-days (others have been negative). Five studies assessed aSyn seeding activity in skin biopsies from PD patients (sensitivity of 86-96%). A single in vivo MSA/PSP study detected seeding activity in 3/5 MSA and 1/2 PSP.

Using post-mortem MSA and PD brains, we developed a novel, rapid RT-QuIC protocol and applied it to detect minute amounts of aSyn seeds from in vivo cervical skin biopsy samples collected from 10 MSA/13 PD/7 PSP/20 HC, and combined the results with serum NfL measurement.

Results

aSYN was detected in 8/10 MSA, 10/13 PD, 1/7 PSP, and 3/20 HC in a single skin biopsy sample (sensitivity 80%/specificity 85% synucleinopathies versus non-synucleinopathies). In 2/5 negative patients with suspected synucleinopathy, a second cervical biopsy was available and increased the sensitivity to 86%(specificity 85%). Combining RT-QuIC with serum NfL (threshold 30pg/ml), achieved 100% sensitivity/100% specificity in distinguishing MSA from PD, and 100%/93% MSA vs PD/PSP/HC.

Conclusions

We report a rapid (24 hours), minimally invasive, 2 step method with high sensitivity (100%)/specificity (93%) for the in vivo diagnosis of MSA compared to PD/PSP/HC (also PD from HC/PSP) using a novel RT-QuIC protocol capable of detecting seeding activity in both PD and MSA.

If replicated, our method has the potential to revolutionize the diagnosis of parkinsonism, and stratification into clinical trials.

Authors/Disclosures
Diana Angelika Olszewska, MD, PhD (Cork University Hospital) PRESENTER	Dr. Olszewska has nothing to disclose.
	No disclosure on file
	No disclosure on file
Mario Sousa, MD (UHN Toronto Western Hospital)	Dr. Sousa has nothing to disclose.
	No disclosure on file
Anna Vasilevskaya, PhD	Anna Vasilevskaya has nothing to disclose.
Chloe Anastassiadis (Tanz Centre for Research on Neurodegenerative Disease)	Ms. Anastassiadis has received research support from Fonds de Recherche du Québec - Santé (FRQS).
Carmela Tartaglia, MD (Toronto Western Hospital, University of Toronto)	Dr. Tartaglia has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. The institution of Dr. Tartaglia has received research support from NIH. The institution of Dr. Tartaglia has received research support from University of Toronto.
	No disclosure on file
Anthony E. Lang, MD, FAAN (Toronto Western Hospital)	Dr. Lang has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for AbbVie, Amylyx, Aprinoia, Biogen, BioAdvance, Biohaven, BioVie, BlueRock, BMS, Denali, Janssen, Lilly, Pharma 2B, Sun Pharma, and UCB. Dr. Lang has received personal compensation in the range of $50,000-$99,999 for serving as an Expert Witness for medicolegal cases related to paraquat. The institution of Dr. Lang has received research support from AbbVie. Dr. Lang has received intellectual property interests from a discovery or technology relating to health care. Dr. Lang has received publishing royalties from a publication relating to health care.

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