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Does Parkinson’s disease start in the gut?

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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.

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Acknowledgements

Work in the Derkinderen lab is supported by France Parkinson, Institut de France, CECAP (Comité d’Entente et de Coordination des Associations de Parkinsoniens), FFGP (Fédération française des groupements parkinsoniens) and Parkinsoniens de Vendée. The Arizona group has been supported by the US National Institute on Aging (P30 AG19610 Arizona Alzheimer’s Disease Core Center), National Institute of Neurological Disorders and Stroke (U24 NS072026 National Brain and Tissue Resource for Parkinson’s Disease and Related Disorders), the Arizona Department of Health Services (contract 211002, Arizona Alzheimer’s Research Center), the Arizona Biomedical Research Commission (contracts 4001, 0011, 05-901 and 1001 to the Arizona Parkinson’s Disease Consortium) and the Michael J. Fox Foundation for Parkinson’s Research”.

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Correspondence to Pascal Derkinderen.

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Lionnet, A., Leclair-Visonneau, L., Neunlist, M. et al. Does Parkinson’s disease start in the gut?. Acta Neuropathol 135, 1–12 (2018). https://doi.org/10.1007/s00401-017-1777-8

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  • DOI: https://doi.org/10.1007/s00401-017-1777-8

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