Pathological α‐synuclein in gastrointestinal tissues from prodromal P arkinson disease patients
Abstract
Objective: It has been hypothesized that Lewy pathology initiates in the enteric nervous system years prior to debut of clinical motor symptoms in Parkinson disease patients. This study investigates whether Lewy pathology is present in various gastrointestinal tract tissues from Parkinson disease patients in the prodromal phase. Methods: We used the Danish National Pathology Registry to identify archived paraffin‐embedded tissue blocks from 57 Parkinson disease patients (98 blocks) and 90 control subjects (98 blocks). We employed 2 different immunohistochemistry techniques visualizing aggregated α‐synuclein and phosphorylated α‐synuclein. Results: Thirty‐nine Parkinson disease patients contributed tissues obtained in the prodromal disease phase, whereas 18 Parkinson disease patients contributed tissues obtained solely after Parkinson diagnosis. Prodromal tissues were obtained on average 7.0 years prior to diagnosis (range = 20 years to 4 months), and postdiagnosis tissue on average 2.8 years after diagnosis (range = 2 days to 18 years). Phosphorylated α‐synuclein positivity was seen in 22 of 39 (56%) prodromal Parkinson disease subjects and 30 of 67 (45%) prodromal tissue blocks. These fractions were significantly higher compared to control subjects ( p = 0.0001 and p = 0.0032, respectively). In contrast, no significant difference was seen in the positivity rate between prodromal Parkinson disease patients and controls when using the aggregated α‐synuclein immunohistochemistry technique. Interpretation: We detected Lewy pathology in the gastrointestinal tract of patients up to 20 years prior to their Parkinson disease diagnosis. These findings are in accordance with a hypothesized prodromal disease phase spanning 10 to 20 years. Ann Neurol 2016;79:940–949
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There is increasing evidence that α-synuclein aggregates are found outside the brain in PD, before the onset of motor symptoms.
“Second, there is increasing evidence that α-synuclein aggregates are found outside the brain in PD, before the onset of motor symptoms [12–14].”
From The gut–brain axis in early Parkinson’s disease: from prodrome to prevention (2025) · cites this paper as [12]
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- Authors
- Stokholm, M. G., Danielsen, E. H., Hamilton‐Dutoit, S. J., & Borghammer, P.
- Affiliations
- Aarhus University Hospital (DK)
- Institute of Pathology Aarhus University Hospital Aarhus Denmark
- Corresponding author
- Stokholm, Morten Gersel
- Venue
- Annals of Neurology
- Publisher
- Wiley
- Published
- 2016-04-09
- Volume
- 79
- Issue
- 6
- Pages
- 940-949
- ISSN
- 0364-5134 (ISSN-L)
- 1531-8249
- OpenAlex
- W2309910088
- Cited by
- 415
- References
- 4
- Citations by year
- 2026: 35 · 2025: 43 · 2024: 34 · 2023: 47 · 2022: 54 · 2021: 55 · 2020: 36 · 2019: 32 · 2018: 33 · 2017: 35 · 2016: 11
- FWCI
- 27.82
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Annals of Neurology (publishedVersion)
- PubMed (publishedVersion)
- Scopus (Elsevier) (submittedVersion)
- Funders
- Riisfort Foundation
- Topics
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nuclear Receptors and Signaling
- Health Sciences › Medicine › Neurology › Neurological disorders and treatments
- Keywords
- Parkinson's disease, prodromal Parkinson's disease, alpha-synuclein, phosphorylated alpha-synuclein, Lewy body pathology, gastrointestinal tract, enteric nervous system, alpha-synuclein aggregation
- MeSH terms
- Adult, Aged, Aged, 80 and over, Female, Humans, Male, Middle Aged, Parkinson Disease, Phosphorylation, Registries, Case-Control Studies, Gastrointestinal Tract, alpha-Synuclein, Prodromal Symptoms
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