Pathological α-synuclein in gastrointestinal tissues from prodromal Parkinson disease patients
- PMID: 27015771
- DOI: 10.1002/ana.24648
Pathological α-synuclein in gastrointestinal tissues from prodromal Parkinson 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.
© 2016 American Neurological Association.
Similar articles
-
Lewy pathological study on α-synuclein in gastrointestinal tissues of prodromal Parkinson's disease.Eur Rev Med Pharmacol Sci. 2017 Apr;21(7):1514-1521. Eur Rev Med Pharmacol Sci. 2017. Retraction in: Eur Rev Med Pharmacol Sci. 2017 May;21(9):2007.. PMID: 28429355 Retracted.
-
Parkinson disease: Peripheral α-synuclein deposits - prodromal markers for Parkinson disease?Nat Rev Neurol. 2016 May;12(5):249. doi: 10.1038/nrneurol.2016.54. Epub 2016 Apr 15. Nat Rev Neurol. 2016. PMID: 27080519 No abstract available.
-
Do subjects with minimal motor features have prodromal Parkinson disease?Ann Neurol. 2018 Mar;83(3):562-574. doi: 10.1002/ana.25179. Epub 2018 Mar 10. Ann Neurol. 2018. PMID: 29420861 Free PMC article.
-
Can we use peripheral tissue biopsies to diagnose Parkinson's disease? A review of the literature.Eur J Neurol. 2016 Feb;23(2):247-61. doi: 10.1111/ene.12753. Epub 2015 Jun 23. Eur J Neurol. 2016. PMID: 26100920 Review.
-
Gut-brain axis and the spread of α-synuclein pathology: Vagal highway or dead end?Mov Disord. 2019 Mar;34(3):307-316. doi: 10.1002/mds.27556. Epub 2019 Jan 17. Mov Disord. 2019. PMID: 30653258 Review.
Cited by
-
Diagnostic accuracy and predictors of alpha-synuclein accumulation in the gastrointestinal tract of Parkinson's disease.NPJ Parkinsons Dis. 2024 Aug 15;10(1):155. doi: 10.1038/s41531-024-00766-3. NPJ Parkinsons Dis. 2024. PMID: 39147801 Free PMC article.
-
Parkinson's disease is associated with low striated esophagus contractility potentially contributing to the development of dysphagia.Neurogastroenterol Motil. 2024 Aug;36(8):e14822. doi: 10.1111/nmo.14822. Epub 2024 May 26. Neurogastroenterol Motil. 2024. PMID: 38798058
-
Safety and efficacy of faecal microbiota transplantation in patients with mild to moderate Parkinson's disease (GUT-PARFECT): a double-blind, placebo-controlled, randomised, phase 2 trial.EClinicalMedicine. 2024 Mar 27;71:102563. doi: 10.1016/j.eclinm.2024.102563. eCollection 2024 May. EClinicalMedicine. 2024. PMID: 38686220 Free PMC article.
-
Immunological aspects of central neurodegeneration.Cell Discov. 2024 Apr 9;10(1):41. doi: 10.1038/s41421-024-00666-z. Cell Discov. 2024. PMID: 38594240 Free PMC article. Review.
-
α-Synuclein: A Promising Biomarker for Parkinson's Disease and Related Disorders.J Mov Disord. 2024 Apr;17(2):127-137. doi: 10.14802/jmd.24075. Epub 2024 Apr 9. J Mov Disord. 2024. PMID: 38589016 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical