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Cited by 1,354Parkinson's Disease Mechanisms and TreatmentsNuclear Receptors and SignalingNeuroinflammation and Neurodegeneration Mechanisms

Gastric α-synuclein immunoreactive inclusions in Meissner's and Auerbach's plexuses in cases staged for Parkinson's disease-related brain pathology

Braak, Heiko, de Vos, Rob A.I., Bohl, Jürgen, Del Tredici, Kelly·2006·Neuroscience Letters
DOI 10.1016/j.neulet.2005.11.012
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Abstract

The progressive degenerative process associated with sporadic Parkinson's disease (sPD) is characterized by formation of alpha-synuclein-containing inclusion bodies in a few types of projection neurons in both the enteric and central nervous systems (ENS and CNS). In the brain, the process apparently begins in the brainstem (dorsal motor nucleus of the vagal nerve) and advances through susceptible regions of the basal mid-and forebrain until it reaches the cerebral cortex. Anatomically, all of the vulnerable brain regions are closely interconnected. Whether the pathological process begins in the brain or elsewhere in the nervous system, however, is still unknown. We therefore used immunocytochemisty to investigate the gastric myenteric and submucosal plexuses in 150 microm cryosections and 8 microm paraffin sections from five autopsy individuals, whose brains were also staged for Parkinson-associated synucleinopathy. alpha-synuclein immunoreactive inclusions were found in neurons of the submucosal Meissner plexus, whose axons project into the gastric mucosa and terminate in direct proximity to fundic glands. These elements could provide the first link in an uninterrupted series of susceptible neurons that extend from the enteric to the central nervous system. The existence of such an unbroken neuronal chain lends support to the hypothesis that a putative environmental pathogen capable of passing the gastric epithelial lining might induce alpha-synuclein misfolding and aggregation in specific cell types of the submucosal plexus and reach the brain via a consecutive series of projection neurons.

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  • During the first stages of Parkinson's disease, neurons of the enteric nervous system and olfactory bulbs contain aggregated and phosphorylated alpha-synuclein.

    “During the first stages of PD, neurons of the ENS and the olfactory bulbs (OB) were found to contain aggregated and phosphorylated alpha-synuclein (Braak et al., 2006;Shannon et al., 2012b).”

    From The Gut-Brain Axis in Parkinson’s Disease: Possibilities for Food-Based Therapies (2017) · cites this paper as Braak et al., 2006

  • Several clinical studies revealed that Parkinson's disease patients expressed alpha-synuclein accumulation in the enteric nervous system.

    “Several clinical studies revealed that PD patients expressed alphasynuclein accumulation in the ENS (Braak et al., 2006;Forsyth et al., 2011;Gelpi et al., 2014;Gold et al., 2013;Sánchez-Ferro et al., 2015;Shannon et al., 2012a).”

    From The Gut-Brain Axis in Parkinson’s Disease: Possibilities for Food-Based Therapies (2017) · cites this paper as Braak et al., 2006

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Authors
Braak, H., de Vos, R. A. I., Bohl, J., & Del Tredici, K.
Affiliations
Goethe University Frankfurt (DE)
Corresponding author
Braak, Heiko
ORCID
Braak, Heiko
Venue
Neuroscience Letters
Publisher
Elsevier BV
Published
2006-03
Volume
396
Issue
1
Pages
67-72
ISSN
0304-3940 (ISSN-L)
DOI
10.1016/j.neulet.2005.11.012
OpenAlex
W2142483035
Semantic Scholar
7f376c4b1f3f257ebbc010f8a10aba2ddeebcdcd
Cited by
1,354
References
33
Citations by year
2026: 61 · 2025: 76 · 2024: 82 · 2023: 83 · 2022: 111 · 2021: 128 · 2020: 92 · 2019: 85 · 2018: 72 · 2017: 81 · 2016: 70 · 2015: 55 · 2014: 59 · 2013: 48 · 2012: 61
FWCI
9.28
Type
journal article
Language
en
Open access
closed
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • Neuroscience Letters (publishedVersion)
  • PubMed (publishedVersion)
Funders
Deutsche Forschungsgemeinschaft
Topics
  • Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nuclear Receptors and Signaling
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Keywords
Parkinson's disease, alpha-synuclein, synucleinopathies, submucosal plexus, myenteric plexus, submucosal neurons, enteric nervous system, brainstem, neurodegeneration
MeSH terms
Aged, Aged, 80 and over, Axonal Transport, Brain, Inclusion Bodies, Female, Gastric Mucosa, Humans, Male, Middle Aged, Models, Neurological, Myenteric Plexus, Nerve Net, Neural Pathways, Neurons, Parkinson Disease, Prions, Submucous Plexus, Vagus Nerve, Protein Folding, Disease Transmission, Infectious, alpha-Synuclein

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