α-synuclein in the appendiceal mucosa of neurologically intact subjects.

Mov Disord. 2013 Dec 18. doi: 10.1002/mds.25779. [Epub ahead of print]

Gray MT, Munoz DG, Gray DA, Schlossmacher MG, Woulfe JM.

Author information

Centre for Cancer Therapeutics, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada; Department of Pathology and Laboratory Medicine, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada; Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada.

Abstract

Parkinson's disease is characterized by the pathological aggregation of α-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.