Journal article
High diagnostic performance of independent alpha-synuclein seed amplification assays for detection of early Parkinson’s disease
Acta neuropathologica communications, Vol.9(1), pp.1-179
11/06/2021
DOI: 10.1186/s40478-021-01282-8
PMCID: PMC8572469
PMID: 34742348
Abstract
AbstractAlpha-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.
Details
- Title: Subtitle
- High diagnostic performance of independent alpha-synuclein seed amplification assays for detection of early Parkinson’s disease
- Creators
- Marco J RussoChristina D OrruLuis Concha-MarambioSimone GiaisiBradley R GrovemanCarly M FarrisBret HolguinAndrew G HughsonDavid-Erick LaFontantChelsea Caspell-GarciaChristopher S CoffeyJennifer MollonSamantha J HuttenKalpana MerchantRoland G HeymClaudio SotoByron CaugheyUn Jung Kang
- Resource Type
- Journal article
- Publication Details
- Acta neuropathologica communications, Vol.9(1), pp.1-179
- DOI
- 10.1186/s40478-021-01282-8
- PMID
- 34742348
- PMCID
- PMC8572469
- NLM abbreviation
- Acta Neuropathol Commun
- ISSN
- 2051-5960
- eISSN
- 2051-5960
- Grant note
- DOI: 10.13039/100000002, name: National Institutes of Health, award: T32AG052909, R01 AG055053; DOI: 10.13039/100000864, name: Michael J. Fox Foundation for Parkinson's Research, award: 16712; DOI: 10.13039/100006492, name: Division of Intramural Research, National Institute of Allergy and Infectious Diseases; DOI: 10.13039/100008440, name: International Parkinson and Movement Disorder Society
- Language
- English
- Date published
- 11/06/2021
- Academic Unit
- Biostatistics
- Record Identifier
- 9984214818702771
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