Does Parkinson’s disease start in the gut?

Arthur Lionnet, Laurène Leclair-Visonneau, Michel Neunlist, Shigeo Murayama, Masaki Takao, Charles Howard Adler, Pascal Derkinderen, Thomas G. Beach

Research output: Contribution to journalArticle

45 Citations (Scopus)

Abstract

Parkinson’s disease (PD) is pathologically characterized by the presence of intraneuronal inclusions, termed Lewy bodies and Lewy neurites, whose main component is alpha-synuclein. Based on the topographic distribution of Lewy bodies and neurites established after autopsy from PD patients, Braak and coworkers hypothesized that PD pathology may start in the gastrointestinal tract then spread through the vagus nerve to the brain. This hypothesis has been reinforced by the discovery that alpha-synuclein may be capable of spreading transcellularly, thereby providing a mechanistic basis for Braak’s hypothesis. This ‘gut to brain’ scenario has ignited heated debates within the movement disorders community and prompted a large number of studies in both humans and animals. Here, we review the arguments for and against the gut as the origin of PD. We conclude that the human autopsy evidence does not support the hypothesis and that it is too early to draw any definitive conclusions. We discuss how this issue might be further addressed in future research.

Original languageEnglish (US)
Pages (from-to)1-12
Number of pages12
JournalActa Neuropathologica
DOIs
StateAccepted/In press - Oct 16 2017

Fingerprint

Parkinson Disease
Lewy Bodies
alpha-Synuclein
Neurites
Autopsy
Vagus Nerve
Movement Disorders
Brain
Gastrointestinal Tract
Pathology

Keywords

  • Alpha-synuclein
  • Dorsal motor nucleus of the vagus
  • Enteric nervous system
  • Gut
  • Parkinson’s disease
  • Vagus nerve

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Clinical Neurology
  • Cellular and Molecular Neuroscience

Cite this

Lionnet, A., Leclair-Visonneau, L., Neunlist, M., Murayama, S., Takao, M., Adler, C. H., ... Beach, T. G. (Accepted/In press). Does Parkinson’s disease start in the gut? Acta Neuropathologica, 1-12. https://doi.org/10.1007/s00401-017-1777-8

Does Parkinson’s disease start in the gut? / Lionnet, Arthur; Leclair-Visonneau, Laurène; Neunlist, Michel; Murayama, Shigeo; Takao, Masaki; Adler, Charles Howard; Derkinderen, Pascal; Beach, Thomas G.

In: Acta Neuropathologica, 16.10.2017, p. 1-12.

Research output: Contribution to journalArticle

Lionnet, A, Leclair-Visonneau, L, Neunlist, M, Murayama, S, Takao, M, Adler, CH, Derkinderen, P & Beach, TG 2017, 'Does Parkinson’s disease start in the gut?', Acta Neuropathologica, pp. 1-12. https://doi.org/10.1007/s00401-017-1777-8
Lionnet A, Leclair-Visonneau L, Neunlist M, Murayama S, Takao M, Adler CH et al. Does Parkinson’s disease start in the gut? Acta Neuropathologica. 2017 Oct 16;1-12. https://doi.org/10.1007/s00401-017-1777-8
Lionnet, Arthur ; Leclair-Visonneau, Laurène ; Neunlist, Michel ; Murayama, Shigeo ; Takao, Masaki ; Adler, Charles Howard ; Derkinderen, Pascal ; Beach, Thomas G. / Does Parkinson’s disease start in the gut?. In: Acta Neuropathologica. 2017 ; pp. 1-12.
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