Alpha‐synuclein in the appendiceal mucosa of neurologically intact subjects

Citations Over TimeTop 10% of 2013 papers

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.

Related Papers

• → The enteric nervous system undergoes significant chemical and synaptic maturation during adolescence in mice(2019)58 cited
• → The tight junction component protein, claudin-4, is expressed by enteric neurons in the rat distal colon(2007)7 cited
• The expression and physiological function of CRF neuron in the myenteric plexus of enteric nervous system of guineapig(2004)
• Localization of CRFl IR Nneurons in the Enteric Nerve System of Guinea Pig(2003)