ArticleCells2021
Seeding Propensity and Characteristics of Pathogenic αSyn Assemblies in Formalin-Fixed Human Tissue from the Enteric Nervous System, Olfactory Bulb, and Brainstem in Cases Staged for Parkinson's Disease.
Article in Cells, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 1 of them a synthesis that pooled it.
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Who cites it
19 citing papers in PubMed, 1 synthesis or guideline pooled it, 27 citations in OpenAlex.
- Alpha-Synuclein Strain Variability in Body-First and Brain-First Synucleinopathies.Frontiers in aging neuroscience · 2022Pooled it
- Activated microglial phenotypes in the hippocampal CA2 subfield are implicated in Lewy body disease progression.Acta neuropathologica · 2026Article
- Microglial reactivity in the hippocampal CA2 is associated with advanced neuronal α-synucleinopathy.bioRxiv : the preprint server for biology · 2026Article
- Enteric nervous system as a therapeutic target in gastrointestinal disorders.World journal of gastrointestinal pharmacology and therapeutics · 2025Article
- Seed Amplification Assay for α-Synuclein: Diagnostic Applications in Synucleinopathies.International journal of molecular sciences · 2025Review
- Alpha-Synuclein Seed Amplification Assays in Parkinson's Disease: A Systematic Review and Network Meta-Analysis.Clinics and practice · 2025Review
- Sympathetic and parasympathetic subtypes of body-first Lewy body disease observed in postmortem tissue from prediagnostic individuals.Nature neuroscience · 2025Article
- Refining α-synuclein seed amplification assays to distinguish Parkinson's disease from multiple system atrophy.Translational neurodegeneration · 2025Article
- N-terminus α-synuclein detection reveals new and more diverse aggregate morphologies in multiple system atrophy and Parkinson's disease.Translational neurodegeneration · 2024Article
- Aptamer binding footprints discriminate α-synuclein fibrillar polymorphs from different synucleinopathies.Nucleic acids research · 2024Article
- Disease Mechanisms of Multiple System Atrophy: What a Parallel Between the Form of Pasta and the Alpha-Synuclein Assemblies Involved in MSA and PD Tells Us.Cerebellum (London, England) · 2024Review
- Parkinson's disease and gut microbiota: from clinical to mechanistic and therapeutic studies.Translational neurodegeneration · 2023Review
- The Impact of Microbiota on the Gut-Brain Axis: Examining the Complex Interplay and Implications.Journal of clinical medicine · 2023Review
- Disease-Specific α-Synuclein Seeding in Lewy Body Disease and Multiple System Atrophy Are Preserved in Formaldehyde-Fixed Paraffin-Embedded Human Brain.Biomolecules · 2023Article
- New protocol for kinetic assay seeding ability recovery "KASAR" from formalin-fixed paraffin-embedded tissues.Frontiers in molecular biosciences · 2023Article
- Gastrointestinal involvement in Parkinson's disease: pathophysiology, diagnosis, and management.NPJ Parkinson's disease · 2022Review
- The Baseline Structure of the Enteric Nervous System and Its Role in Parkinson's Disease.Life (Basel, Switzerland) · 2021Review
- Vagus Nerve and Stomach Synucleinopathy in Parkinson's Disease, Incidental Lewy Body Disease, and Normal Elderly Subjects: Evidence Against the "Body-First" Hypothesis.Journal of Parkinson's disease · 2021Article
- The α-Synuclein Origin and Connectome Model (SOC Model) of Parkinson's Disease: Explaining Motor Asymmetry, Non-Motor Phenotypes, and Cognitive Decline.Journal of Parkinson's disease · 2021Review
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
We investigated α-synuclein's (αSyn) seeding activity in tissue from the brain and enteric nervous system. Specifically, we assessed the seeding propensity of pathogenic αSyn in formalin-fixed tissue from the gastric cardia and five brain regions of 29 individuals (12 Parkinson's disease, 8 incidental Lewy body disease, 9 controls) using a protein misfolding cyclic amplification assay. The structural characteristics of the resultant αSyn assemblies were determined by limited proteolysis and transmission electron microscopy. We show that fixed tissue from Parkinson's disease (PD) and incidental Lewy body disease (ILBD) seeds the aggregation of monomeric αSyn into fibrillar assemblies. Significant variations in the characteristics of fibrillar assemblies derived from different regions even within the same individual were observed. This finding suggests that fixation stabilizes seeds with an otherwise limited seeding propensity, that yield assemblies with different intrinsic structures (i.e., strains). The lag phase preceding fibril assembly for patients ≥80 was significantly shorter than in other age groups, suggesting the existence of increased numbers of seeds or a higher seeding potential of pathogenic αSyn with time. Seeding activity did not diminish in late-stage disease. No statistically significant difference in the seeding efficiency of specific regions was found, nor was there a relationship between seeding efficiency and the load of pathogenic αSyn in a particular region at a given neuropathological stage.
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