ArticleActa neuropathologica communications2021
High diagnostic performance of independent alpha-synuclein seed amplification assays for detection of early Parkinson's disease.
Article in Acta neuropathologica communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 155 papers, 5 of them syntheses that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
155 citing papers in PubMed, 5 syntheses or guidelines pooled it, 245 citations in OpenAlex.
- Cerebrospinal Fluid Biomarkers of NLRP3 Pathway, Immune Dysregulation, and Neurodegeneration in Parkinson's Disease: A Meta-Analysis.Movement disorders : official journal of the Movement Disorder Society · 2026Pooled it
- Diagnostic biomarkers for α-synucleinopathies- state of the art and future developments: a systematic review.Molecular neurodegeneration · 2025Pooled it
- Cerebrospinal fluid biomarkers for diagnosis of Parkinson's disease: a systematic review and network meta-analysis.Journal of neurology · 2025Pooled it
- Biofluid Detection of Pathological α-Synuclein in the Prodromal Phase of Synucleinopathies.Journal of Parkinson's disease · 2024Pooled it
- Alpha-Synuclein Strain Variability in Body-First and Brain-First Synucleinopathies.Frontiers in aging neuroscience · 2022Pooled it
- From a prion seed to a tree of discoveries: Byron Caughey's RT-QuIC legacy in protein misfolding research.Acta neuropathologica · 2026Review
- Probing the Energy Landscape of α-Synuclein Amyloid Fibril Formation by Systematic K-to-Q Mutagenesis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Lasker~Bloomberg Public Service Award to Michael J. Fox: The challenge of Parkinson's disease.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Detection of α-synuclein seeding activity in tear fluid as a candidate biomarker for Parkinson's disease.Journal of Parkinson's disease · 2026Article
- Identification and validation of Parkinson's disease relevant microRNAs in plasma extracellular vesicles.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2026Article
- Inter-assay and Inter-site Performance of Alpha-Synuclein Seed Amplification Assays in Synucleinopathies: A Multicenter 2 × 2 Protocol Comparison.Neurology and therapy · 2026Article
- Advances in biomarkers for Parkinson's disease: from molecular pathology to precision diagnostics.Journal of Zhejiang University. Science. B · 2026Review
- Genetic and Pathological Testing Attitudes for Parkinson's Disease in At-Risk Relatives.Movement disorders clinical practice · 2026Article
- Reframing welders' parkinsonism: from the "idiopathic" label to biological causation and legal recognition.Annals of occupational and environmental medicine · 2026Review
- Preparing for Parkinson's disease prevention trials: Current progress and future directions.Journal of Parkinson's disease · 2026Review
- Gaps in the Parkinson's disease therapeutic clinical pipeline: A focus on approaches targeting disease pathobiology.Journal of Parkinson's disease · 2026Review
- Biomarkers stewardship in parkinsonism: integrating alpha-synuclein seed amplification assays and neurofilament light chain into diagnostic pathways and patient communication.Journal of neurology · 2026Review
- Synucleinopathy-like clinical features and biologically defined synuclein seeding in PSP-Parkinsonism: an imperfect match.NPJ Parkinson's disease · 2026Article
- A Systematic Comparison of Alpha-Synuclein Seed Amplification Assays for Increasing Reproducibility.Annals of clinical and translational neurology · 2026Review
- Body Fluid-based Biomarkers for Cognitive Impairment in Parkinson's Disease.Annals of neurosciences · 2026Review
95 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
18 authors at 9 institutions in 2 countries.
Funding
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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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.