Duodenal alpha‐Synuclein Pathology and Enteric Gliosis in Advanced Parkinson's Disease

• Published in: Movement disorders Vol. 38; no. 5; pp. 885 - 894
• Main Authors: Emmi, Aron, Sandre, Michele, Russo, Francesco Paolo, Tombesi, Giulia, Garrì, Federica, Campagnolo, Marta, Carecchio, Miryam, Biundo, Roberta, Spolverato, Gaya, Macchi, Veronica, Savarino, Edoardo, Farinati, Fabio, Parchi, Piero, Porzionato, Andrea, Bubacco, Luigi, De Caro, Raffaele, Kovacs, Gabor G., Antonini, Angelo
• Format: Journal Article
• Language: English
• Published: Hoboken, USA John Wiley & Sons, Inc 01.05.2023; Wiley Subscription Services, Inc
• Subjects: alpha-Synuclein - metabolism; alpha‐synuclein; Antibodies; Biopsy; Cell size; Duodenum; Duodenum - chemistry; Duodenum - metabolism; Duodenum - pathology; Endoscopy; Enteric nervous system; gastrointestinal biopsies; Glial cells; Glial fibrillary acidic protein; Glial Fibrillary Acidic Protein - metabolism; Gliosis; Gut-brain axis; Humans; Immunohistochemistry; Levodopa; Movement disorders; Neurodegenerative diseases; Neuronal-glial interactions; neuropathology; Ostomy; Parkinson Disease - pathology; Parkinson's disease; Pathology; Proteins; Small intestine; Synuclein; Tubulin; gastrointestinal biopsies; Parkinson's disease; enteric nervous system; alpha-synuclein; neuropathology
• DOI: 10.1002/mds.29358
• ISSN: 0885-3185; 1531-8257

Background The role of the gut‐brain axis has been recently highlighted as a major contributor to Parkinson's disease (PD) physiopathology, with numerous studies investigating bidirectional transmission of pathological protein aggregates, such as α‐synuclein (αSyn). However, the extent and the characteristics of pathology in the enteric nervous system have not been fully investigated. Objective We characterized αSyn alterations and glial responses in duodenum biopsies of patients with PD by employing topography‐specific sampling and conformation‐specific αSyn antibodies. Methods We examined 18 patients with advanced PD who underwent Duodopa percutaneous endoscopic gastrostomy and jejunal tube procedure, 4 untreated patients with early PD (disease duration <5 years), and 18 age‐ and ‐sex‐matched healthy control subjects undergoing routine diagnostic endoscopy. A mean of four duodenal wall biopsies were sampled from each patient. Immunohistochemistry was performed for anti‐aggregated αSyn (5G4) and glial fibrillary acidic protein antibodies. Morphometrical semiquantitative analysis was performed to characterize αSyn‐5G4+ and glial fibrillary acidic protein–positive density and size. Results Immunoreactivity for aggregated α‐Syn was identified in all patients with PD (early and advanced) compared with controls. αSyn‐5G4+ colocalized with neuronal marker β‐III‐tubulin. Evaluation of enteric glial cells demonstrated an increased size and density when compared with controls, suggesting reactive gliosis. Conclusions We found evidence of synuclein pathology and gliosis in the duodenum of patients with PD, including early de novo cases. Future studies are required to evaluate how early in the disease process duodenal pathology occurs and its possible contribution to levodopa effect in chronic patients. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.