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Alpha-synuclein in the appendiceal mucosa of neurologically intact subjects

Authors

  • Madison T. Gray BSc,

    1. Centre for Cancer Therapeutics, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada
    2. Department of Pathology and Laboratory Medicine, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada
    3. Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada
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  • David G. Munoz MD, MSc, FRCP(C),

    1. Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada
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  • Douglas A. Gray PhD,

    1. Centre for Cancer Therapeutics, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada
    2. Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada
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  • Michael G. Schlossmacher MD, FRCP(C),

    1. Division of Neuroscience, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada
    2. Division of Neurology, The Ottawa Hospital, Ottawa, Ontario, Canada
    3. Department of Medicine, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada
    4. Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada
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  • John M. Woulfe MD, PhD, FRCP(C)

    Corresponding author
    1. Centre for Cancer Therapeutics, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada
    2. Department of Pathology and Laboratory Medicine, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada
    3. Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada
    4. Department of Pathology and Laboratory Medicine, The Ottawa Hospital, Ottawa, Ontario, Canada
    • Correspondence to: Dr. John M. Woulfe, Centre for Cancer Therapeutics, Ottawa Hospital Research Institute, Box 926, 501 Smyth Road, Ottawa, Ontario, Canada; jwoulfe@ottawahospital.on.ca

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  • Funding agencies: The Parkinson's Society of Canada and the Ottawa Parkinson's Research Consortium

  • Relevant conflicts of interest/financial disclosures: Nothing to report.

  • Full financial disclosures and author roles may be found in the online version of this article.

ABSTRACT

Parkinson's disease is characterized by the pathological aggregation of Alpha-synuclein. The dual-hit hypothesis proposed by Braak implicates the enteric nervous system as an initial site of α-synuclein aggregation with subsequent spread to the central nervous system. Regional variations in the spatial pattern or levels of α-synuclein along the enteric nervous system could have implications for identifying sites of onset of this pathogenic cascade. We performed immunohistochemical staining for α-synuclein on gastrointestinal tissue from patients with no history of neurological disease using the established LB509 antibody and a new clone, MJFR1, characterized for immunohistochemistry here. We demonstrate that the vermiform appendix is particularly enriched in α-synuclein–containing axonal varicosities, concentrated in its mucosal plexus rather than the classical submucosal and myenteric plexuses. Unexpectedly, intralysosomal accumulations of α-synuclein were detected within mucosal macrophages of the appendix. The abundance and accumulation of α-synuclein in the vermiform appendix implicate it as a candidate anatomical locus for the initiation of enteric α-synuclein aggregation and permits the generation of testable hypotheses for Parkinson's disease pathogenesis. © 2013 International Parkinson and Movement Disorder Society

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