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Open Access 01-12-2021 | Parkinson's Disease | Research

High diagnostic performance of independent alpha-synuclein seed amplification assays for detection of early Parkinson’s disease

Authors: Marco J. Russo, Christina D. Orru, Luis Concha-Marambio, Simone Giaisi, Bradley R. Groveman, Carly M. Farris, Bret Holguin, Andrew G. Hughson, David-Erick LaFontant, Chelsea Caspell-Garcia, Christopher S. Coffey, Jennifer Mollon, Samantha J. Hutten, Kalpana Merchant, Roland G. Heym, Claudio Soto, Byron Caughey, Un Jung Kang

Published in: Acta Neuropathologica Communications | Issue 1/2021

Abstract

Alpha-synuclein seed amplification assays (αSyn-SAAs) are promising diagnostic tools for Parkinson’s disease (PD) and related synucleinopathies. They enable detection of seeding-competent alpha-synuclein aggregates in living patients and have shown high diagnostic accuracy in several PD and other synucleinopathy patient cohorts. However, there has been confusion about αSyn-SAAs for their methodology, nomenclature, and relative accuracies when performed by various laboratories. We compared αSyn-SAA results obtained from three independent laboratories to evaluate reproducibility across methodological variations. We utilized the Parkinson’s Progression Markers Initiative (PPMI) cohort, with DATSCAN data available for comparison, since clinical diagnosis of early de novo PD is critical for neuroprotective trials, which often use dopamine transporter imaging to enrich their cohorts. Blinded cerebrospinal fluid (CSF) samples for a randomly selected subset of PPMI subjects (30 PD, 30 HC, and 20 SWEDD), from both baseline and year 3 collections for the PD and HC groups (140 total CSF samples) were analyzed in parallel by each lab according to their own established and optimized αSyn-SAA protocols. The αSyn-SAA results were remarkably similar across laboratories, displaying high diagnostic performance (sensitivity ranging from 86 to 96% and specificity from 93 to 100%). The assays were also concordant for samples with results that differed from clinical diagnosis, including 2 PD patients determined to be clinically inconsistent with PD at later time points. All three assays also detected 2 SWEDD subjects as αSyn-SAA positive who later developed PD with abnormal DAT-SPECT. These multi-laboratory results confirm the reproducibility and value of αSyn-SAA as diagnostic tools, illustrate reproducibility of the assay in expert hands, and suggest that αSyn-SAA has potential to provide earlier diagnosis with comparable or superior accuracy to existing methods.

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Title: High diagnostic performance of independent alpha-synuclein seed amplification assays for detection of early Parkinson’s disease
Authors: Marco J. Russo
Christina D. Orru
Luis Concha-Marambio
Simone Giaisi
Bradley R. Groveman
Carly M. Farris
Bret Holguin
Andrew G. Hughson
David-Erick LaFontant
Chelsea Caspell-Garcia
Christopher S. Coffey
Jennifer Mollon
Samantha J. Hutten
Kalpana Merchant
Roland G. Heym
Claudio Soto
Byron Caughey
Un Jung Kang
Publication date: 01-12-2021
Publisher: BioMed Central
Keyword: Parkinson's Disease
Published in: Acta Neuropathologica Communications / Issue 1/2021
Electronic ISSN: 2051-5960
DOI: https://doi.org/10.1186/s40478-021-01282-8

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High diagnostic performance of independent alpha-synuclein seed amplification assays for detection of early Parkinson’s disease

Abstract

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

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