In vivo gastric detection of α-synuclein inclusions in Parkinson's disease
Abstract
α-Synuclein inclusions have been identified in the brain and some parts of the enteric nervous system in Parkinson's disease cases. We aimed to assess these inclusions in gastric mucosa samples from patients with symptomatic Parkinson's disease. Random biopsies were performed by gastroscopy in 28 patients with Parkinson's disease and in 29 age- and sex-matched controls. Gastroscopy was performed to start enteral levodopa (L-dopa) therapy in cases and for diagnostic purposes in controls (gastroesophageal reflux, anemia, and abdominal pain were the main indications). The clinical definition of cases and controls was made a priori. Six controls had data suggestive of "mild presymptomatic parkinsonism". Biopsy specimens were immunostained for α-synuclein. The neuropathological diagnosis was established post hoc. No differences were found in the baseline characteristics of the groups. Positive fibers for the α-synuclein protein were observed in 17 of 28 (60.7%) Parkinson's disease patients, 1 of 23 controls (4.3%), and 1 of 6 (16.7%) cases of incident "mild presymptomatic parkinsonism." Neuropathological diagnosis based on α-synuclein immunostaining showed a sensitivity of 85% (95% confidence interval [CI] 62.1-96.8), specificity of 95% (95% CI 76.2-99.9) and area under the receiver operating characteristics curve (AUC) of 0.90 (95% CI 0.80-1.00). No adverse events occurred. Detection of α-synuclein inclusions in the gastric mucosa is a useful and safe tool providing in vivo evidence of the underlying neurodegenerative peripheral involvement linked to Parkinson's disease. Further studies are warranted to determine its pathophysiological implications.
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Alpha-synuclein accumulations are associated with damage in enteric neurons and possibly underlie gastrointestinal dysfunction.
“Alpha-synuclein accumulations are associated with damage in the enteric neurons and possibly underlie GI dysfunction (Gold et al., 2013;Sánchez-Ferro et al., 2015).”
From The Gut-Brain Axis in Parkinson’s Disease: Possibilities for Food-Based Therapies (2017) · cites this paper as Sánchez-Ferro et al., 2015
Abnormalities of gastrointestinal motility might increase the occurrence of small intestinal bacterial overgrowth, which is highly prevalent in Parkinson's disease patients, even in recently diagnosed patients.
“Abnormalities of GI motility might increase the occurrence of SIBO which is highly prevalent in PD patients (Brown et al., 2011;Sánchez-Ferro et al., 2015), even in recently diagnosed PD patients (Tan et al., 2014).”
From The Gut-Brain Axis in Parkinson’s Disease: Possibilities for Food-Based Therapies (2017) · cites this paper as Sánchez-Ferro et al., 2015
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Overexpression-Induced α-Synuclein Brain Spreading
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Optimizing Western Blots for the Detection of Endogenous α-Synuclein in the Enteric Nervous System
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- Authors
- Sánchez‐Ferro, Á., Rábano, A., Catalán, M. J., Rodríguez‐Valcárcel, F. C., Díez, S. F., Herreros‐Rodríguez, J., García‐Cobos, E., Álvarez‐Santullano, M. M., López‐Manzanares, L., Mosqueira, A. J., Desojo, L. V., López‐Lozano, J. J., López‐Valdés, E., Sánchez‐Sánchez, R., & Molina‐Arjona, J. A.
- Affiliations
- Universidad Complutense de Madrid (ES)
- Fundacion Centro De Investigacion De Enfermedades Neurologicas (ES)
- Hospital Universitario 12 De Octubre (ES)
- Department of Neurology Hospital Universitario 12 de Octubre Madrid Spain
- Movement Disorders Unit Department of Neurology Hospital Universitario Puerta del Hierro Madrid Spain
- Hospital Universitario Puerta de Hierro Majadahonda (ES)
- Hospital Universitario de La Princesa (ES)
- Department of Neurology Fundación Hospital Alcorcón Alcorcón, Madrid Spain
- Hospital Universitario Reina Sofía (ES)
- Corresponding author
- Sánchez‐Ferro, Álvaro
- ORCID
- Venue
- Movement Disorders
- Publisher
- Wiley
- Published
- 2014-08-11
- Volume
- 30
- Issue
- 4
- Pages
- 517-524
- ISSN
- 0885-3185 (ISSN-L)
- 1531-8257
- OpenAlex
- W1577379604
- Cited by
- 123
- References
- 41
- Citations by year
- 2026: 5 · 2025: 7 · 2024: 5 · 2023: 9 · 2022: 15 · 2021: 15 · 2020: 7 · 2019: 12 · 2018: 14 · 2017: 13 · 2016: 9 · 2015: 11 · 2014: 1
- FWCI
- 7.39
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Movement Disorders (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Health Sciences › Medicine › Neurology › Neurological disorders and treatments
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nuclear Receptors and Signaling
- Keywords
- Parkinson's disease, alpha-synuclein inclusions, gastric mucosa, enteric nervous system, immunostaining, sensitivity and specificity
- MeSH terms
- Aged, Aged, 80 and over, Female, Gastric Mucosa, Humans, Male, Parkinson Disease, Case-Control Studies, alpha-Synuclein
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