ArticleJournal of Parkinson's disease2021
Vagus Nerve and Stomach Synucleinopathy in Parkinson's Disease, Incidental Lewy Body Disease, and Normal Elderly Subjects: Evidence Against the "Body-First" Hypothesis.
Article in Journal of Parkinson's disease, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers, 1 of them a synthesis that pooled it.
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Who cites it
47 citing papers in PubMed, 1 synthesis or guideline pooled it, 67 citations in OpenAlex.
- Possible linking and treatment between Parkinson's disease and inflammatory bowel disease: a study of Mendelian randomization based on gut-brain axis.Journal of translational medicine · 2025Pooled it
- Co- and Multi-Pathologies in Parkinson's Disease: An International Parkinson and Movement Disorder Society Scientific Issues Committee Review.Movement disorders : official journal of the Movement Disorder Society · 2026Review
- Gut-Brain Signaling in Parkinson's Disease: A Narrative Review.International journal of molecular sciences · 2026Review
- Dynamic thermodynamic-informational entropic relationship (TIER) models of selective vulnerability to neurodegeneration.bioRxiv : the preprint server for biology · 2026Article
- Brain-Only Versus GI-Only Synucleinopathy: A Comprehensive Autopsy Study With Both IHC and SAA.medRxiv : the preprint server for health sciences · 2026Article
- Alpha-Synuclein in Neurodegeneration: From Shared Biology to Disease-Specific Phenotypes.Cells · 2026Review
- A Pathophysiological Model of Parkinson's Disease Based on Microvascular Flow Disturbance and Leukocyte-Mediated Oxidative Injury in Critical Pigmented Neuronal Niches.Antioxidants (Basel, Switzerland) · 2026Article
- The ketogenic diet in Parkinson's disease: a potential therapeutic strategy.Pharmacological reports : PR · 2025Review
- Neuropathology of Lewy body dementia: Lewy-related pathology, α-synuclein oligomers, and comorbid pathologies.Molecular neurodegeneration · 2025Review
- Fasting and postprandial Ghrelin levels in Parkinson's disease: a systematic review and meta-analysis.NPJ Parkinson's disease · 2025Article
- Autonomic dysfunction in neurodegenerative disease.Nature reviews. Neuroscience · 2025Review
- α-Synuclein in Parkinson's Disease: From Bench to Bedside.Medicinal research reviews · 2025Review
- Parkinson's disease beyond the brain: implications for treatments.Frontiers in aging neuroscience · 2025Review
- Biomarker-Based Approach to α-Synucleinopathies: Lessons from Neuropathology.Movement disorders : official journal of the Movement Disorder Society · 2024Article
- Review
- Research Priorities on the Role of α-Synuclein in Parkinson's Disease Pathogenesis.Movement disorders : official journal of the Movement Disorder Society · 2024Review
- Disease progression modelling reveals heterogeneity in trajectories of Lewy-type α-synuclein pathology.Nature communications · 2024Article
- Ultrastructural localization of Porphyromonas gingivalis gingipains in the substantia nigra of Parkinson's disease brains.NPJ Parkinson's disease · 2024Article
- Overlaps and divergences between tauopathies and synucleinopathies: a duet of neurodegeneration.Translational neurodegeneration · 2024Review
- Symmetry of synuclein density in autopsied Parkinson's disease submandibular glands.Neuroscience letters · 2024Article
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundBraak and others have proposed that Lewy-type α-synucleinopathy in Parkinson's disease (PD) may arise from an exogenous pathogen that passes across the gastric mucosa and then is retrogradely transported up the vagus nerve to the medulla.
objectiveWe tested this hypothesis by immunohistochemically staining, with a method specific for p-serine 129 α-synuclein (pSyn), stomach and vagus nerve tissue from an autopsy series of 111 normal elderly subjects, 33 with incidental Lewy body disease (ILBD) and 53 with PD.
methodsVagus nerve samples were taken adjacent to the carotid artery in the neck. Stomach samples were taken from the gastric body, midway along the greater curvature. Formalin-fixed paraffin-embedded sections were immunohistochemically stained for pSyn, shown to be highly specific and sensitive for α-synuclein pathology.
resultsMedian disease duration for the PD group was 13 years. In the vagus nerve none of the 111 normal subjects had pSyn in the vagus, while 12/26 ILBD (46%) and 32/36 PD (89%) subjects were pSyn-positive. In the stomach none of the 102 normal subjects had pSyn while 5/30 (17%) ILBD and 42/52 (81%) of PD subjects were pSyn-positive.
conclusionAs there was no pSyn in the vagus nerve or stomach of subjects without brain pSyn, these results support initiation of pSyn in the brain. The presence of pSyn in the vagus nerve and stomach of a subset of ILBD cases indicates that synucleinopathy within the peripheral nervous system may occur, within a subset of individuals, at preclinical stages of Lewy body disease.
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