Does Parkinson’s disease start in the gut?

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

Research output: Contribution to journalReview article

56 Scopus citations

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)
JournalActa neuropathologica
Volume135
Issue number1
DOIs
StatePublished - Jan 1 2018

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

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  • Cite this

    Lionnet, A., Leclair-Visonneau, L., Neunlist, M., Murayama, S., Takao, M., Adler, C. H., Derkinderen, P., & Beach, T. G. (2018). Does Parkinson’s disease start in the gut? Acta neuropathologica, 135(1). https://doi.org/10.1007/s00401-017-1777-8