ReviewNature protocols2023
Seed amplification assay for the detection of pathologic alpha-synuclein aggregates in cerebrospinal fluid.
Review in Nature protocols, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 148 papers.
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Who cites it
148 citing papers in PubMed, 218 citations in OpenAlex.
- Phase 1, randomized trials of MEDI1341: cerebrospinal fluid free α-synuclein lowered by >50.Brain communications · 2025Trial
- Target engagement and immunogenicity of an active immunotherapeutic targeting pathological α-synuclein: a phase 1 placebo-controlled trial.Nature medicine · 2024Trial
- Research advances in the microbiota‑gut‑brain axis and Parkinson's disease (Review).Molecular medicine reports · 2026Review
- microRNA-7-5p and α-Synuclein SAA Predict Parkinson's Disease Phenoconversion.Annals of clinical and translational neurology · 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
- Article
- Peripheral blood transcriptomic signature is associated with cognitive impairment and freezing of gait in Parkinson's disease: a data-driven approach.NPJ Parkinson's disease · 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
- Diffusion MRI and α-Synuclein Seed Amplification Status in Parkinson's Disease.Annals of neurology · 2026Article
- Advances in biomarkers for Parkinson's disease: from molecular pathology to precision diagnostics.Journal of Zhejiang University. Science. B · 2026Review
- Modeling Parkinson's pathology in human iPSC dopaminergic neurons uncovers key mechanisms of Lewy body formation and heterogeneity.Science advances · 2026Article
- Genome-wide association studies identify genetic determinants of synucleinopathy biomarkers.Research square · 2026Article
- Deep learning-based MRI analysis reveals Lewy body co-pathology accelerates brain aging in Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Clustering Algorithm Reveals Dopamine-Motor Mismatch in Cognitively Preserved Parkinson's Disease.Annals of clinical and translational neurology · 2026Article
- Enrichment and amplification of secreted α-synuclein from cellular model and saliva of patients with synucleinopathies.Biophysics reports · 2026Article
- A Systematic Comparison of Alpha-Synuclein Seed Amplification Assays for Increasing Reproducibility.Annals of clinical and translational neurology · 2026Review
- From phenotype to biology: a multi-modal roadmap of biofluid, tissue, imaging, and digital biomarkers in Parkinson's disease.Translational neurodegeneration · 2026Review
- Detecting the seeds of Parkinson's disease: the evolution of α‑synuclein seed amplification assay as a clinical biomarker.Journal of neural transmission (Vienna, Austria : 1996) · 2026Review
- Discordance of Dopaminergic Dysfunction and Subcortical Atrophy by α-Synuclein Status in Sporadic and Genetic Parkinson's Disease.Movement disorders : official journal of the Movement Disorder Society · 2026Article
- Evaluating the Role of α-Synuclein Seed Amplification as a Disease Progression Marker: Evidence and Uncertainties.Movement disorders clinical practice · 2026Article
88 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Misfolded alpha-synuclein (αSyn) aggregates are a hallmark event in Parkinson's disease (PD) and other synucleinopathies. Recently, αSyn seed amplification assays (αSyn-SAAs) have shown promise as a test for biochemical diagnosis of synucleinopathies. αSyn-SAAs use the intrinsic self-replicative nature of misfolded αSyn aggregates (seeds) to multiply them in vitro. In these assays, αSyn seeds circulating in biological fluids are amplified by a cyclical process that includes aggregate fragmentation into smaller self-propagating seeds, followed by elongation at the expense of recombinant αSyn (rec-αSyn). Amplification of the seeds allows detection by fluorescent dyes specific for amyloids, such as thioflavin T. Several αSyn-SAA reports have been published in the past under the names 'protein misfolding cyclic amplification' (αSyn-PMCA) and 'real-time quaking-induced conversion'. Here, we describe a protocol for αSyn-SAA, originally reported as αSyn-PMCA, which allows detection of αSyn aggregates in cerebrospinal fluid samples from patients affected by PD, dementia with Lewy bodies or multiple-system atrophy (MSA). Moreover, this αSyn-SAA can differentiate αSyn aggregates from patients with PD versus those from patients with MSA, even in retrospective samples from patients with pure autonomic failure who later developed PD or MSA. We also describe modifications to the original protocol introduced to develop an optimized version of the assay. The optimized version shortens the assay length, decreases the amount of rec-αSyn required and reduces the number of inconclusive results. The protocol has a hands-on time of ~2 h per 96-well plate and can be performed by personnel trained to perform basic experiments with specimens of human origin.
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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.