α-Synuclein in the Mucosa of the Human Vermiform Appendix
Madison T Gray, David G Munoz, Douglas A Gray, John M Woulfe. Ottawa Hospital Research Institute, Ottawa, ON, Canada; University of Ottawa, Ottawa, ON, Canada; University of Toronto, Toronto, ON, Canada
Background: Aggregation of α-synuclein (α-syn) in Parkinson's disease (PD) has been hypothesised to begin in the olfactory bulb and the enteric nervous system (ENS) before propagating to the central nervous system. It is still unknown where exactly ENS pathology may begin. The aim of this study was to evaluate the distribution of normal and aberrantly phosphorylated (Ser129) α-syn within the human gastrointestinal tract.
Design: Archival tissues were obtained from patients with no history of synucleinopathy. Intestinal tissue was retrieved from 5 patients who underwent right hemicolectomy for carcinoma resection (average age = 76, range= 67-90). Gastric tissue comes from 5 different patients who received subtotal gastrectomy for various reasons (average age= 61, range=56-70). Relative α-syn expression in tissues was determined by IHC. Identity of α-syn stained structures was determined by immunofluorescence double-labeling.
Results: Vermiform appendix is easily distinguished from other tissue by the plentiful nerve fibres of the mucosal plexus in the lamina propria which exihibit strong α-syn staining. Within the mucosal plexus of the appendix, there is further differential staining with a fine reticular pattern in the apical lamina propria representing the villus subplexus and denser basal staining in the pericryptal and external lamina subplexus. The laminae propriae of the stomach, terminal ileum and colon exhibit only rare α-syn positive nerve fibres. Inclusions of phosphorylated Ser129 α-syn are noted in the mucosa of all appendices examined and were also present in submucosal and myenteric ganglia.
Conclusions: α-syn positive nerve fibres are abundant in the lamina propria of the vermiform appendix, contrasting with the relative scarcity in the stomach, terminal ileum and colon. This holds implications for the initiation of α-syn aggregation in the ENS and possibly the pathogenesis of PD. Given the large immune component of the vermiform appendix, this may provide support for immune-related hypotheses of PD etiology.
Wednesday, March 6, 2013 1:00 PM
Poster Session VI # 255, Wednesday Afternoon