Abstract Details

Title ?-Synuclein in the Mucosa of the Human Vermiform Appendix

Topic Movement Disorders

Presentation(s) P03 - (-)

Poster/Presentation
Number 069

Objective

Background BACKGROUND: Aggregation of ?-synuclein (?-syn) in Parkinson's disease (PD) has been hypothesised to begin in the olfactory bulb and the enteric nervous system (ENS) before propagating via vagal efferents to the CNS.

Design/Methods DESIGN/METHODS: Archival tissues obtained from patients with no history of synucleinopathy included five who underwent right hemicolectomy for carcinoma (average age = 76, range= 67-90) and five who received subtotal gastrectomy for various reasons (average age= 61, range=56-70). Relative ?-syn expression was determined by IHC using mouse monoclonal anti-?-synuclein clone LB509 and phospho-Ser129 ?-syn expression was determined using a rabbit polyclonal antibody.

Results RESULTS: Vermiform appendix was easily distinguished from other tissues by the plentiful nerve fibres of the mucosal plexus in the lamina propria exhibiting intense ?-syn staining. Within the mucosal plexus of the appendix, there was 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 exhibited only rare ?-syn positive nerve fibres. Inclusions of phospho-Ser129 ?-syn were noted in all appendices examined, both in the mucosa of and submucosal and myenteric ganglia.

Conclusions CONCLUSIONS: The lamina propria of the vermiform appendix has an abundant network of ?-syn positive nerve fibres which is absent or under-developed in other GI tissues studied. Inclusions of phosphorylated Ser129 ?-syn within this network suggest possible pathological involvement of the appendix. This provides the setting for further study of the initiation of ?-syn aggregation in the ENS and PD pathogenesis. Given the large immune component of the vermiform appendix, this may provide support for immune-related hypotheses of PD etiology.

Authors/Disclosures
PRESENTER	No disclosure on file
David G. Munoz, MD (University of Toronto)	No disclosure on file
	No disclosure on file
Henry L. Paulson, MD, PhD, FAAN (University of Michigan)	Dr. Paulson has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Exicure. The institution of Dr. Paulson has received research support from National Institutes of Health. Dr. Paulson has a non-compensated relationship as a Member, Nominating committee with American Neurological Association that is relevant to AAN interests or activities.
Henry L. Paulson, MD, PhD, FAAN (University of Michigan)	Dr. Paulson has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Exicure. The institution of Dr. Paulson has received research support from National Institutes of Health. Dr. Paulson has a non-compensated relationship as a Member, Nominating committee with American Neurological Association that is relevant to AAN interests or activities.
John Woulfe (Hamilton General Hospital)	No disclosure on file
	No disclosure on file

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