Immune landscape of the enteric nervous system differentiates Parkinson's disease patients from controls: The PADUA-CESNE cohort

Marta Campagnolo; Luca Weis; Michele Sandre; Aleksandar Tushevski; Francesco Paolo Russo; Edoardo Savarino; Miryam Carecchio; Elena Stocco; Veronica Macchi; Raffaele De Caro; Piero Parchi; Luigi Bubacco; Andrea Porzionato; Angelo Antonini; Aron Emmi

Neurobiology of Disease (Oct 2024)

Immune landscape of the enteric nervous system differentiates Parkinson's disease patients from controls: The PADUA-CESNE cohort

Marta Campagnolo,
Luca Weis,
Michele Sandre,
Aleksandar Tushevski,
Francesco Paolo Russo,
Edoardo Savarino,
Miryam Carecchio,
Elena Stocco,
Veronica Macchi,
Raffaele De Caro,
Piero Parchi,
Luigi Bubacco,
Andrea Porzionato,
Angelo Antonini,
Aron Emmi

Affiliations

Marta Campagnolo: Parkinson and Movement Disorders Unit, Centre for Rare Neurological Diseases (ERN-RND), Department of Neuroscience, University of Padova, Padova, Italy; Center for Neurodegenerative Disease Research (CESNE), University of Padova, Padova, Italy
Luca Weis: Parkinson and Movement Disorders Unit, Centre for Rare Neurological Diseases (ERN-RND), Department of Neuroscience, University of Padova, Padova, Italy
Michele Sandre: Parkinson and Movement Disorders Unit, Centre for Rare Neurological Diseases (ERN-RND), Department of Neuroscience, University of Padova, Padova, Italy
Aleksandar Tushevski: Parkinson and Movement Disorders Unit, Centre for Rare Neurological Diseases (ERN-RND), Department of Neuroscience, University of Padova, Padova, Italy
Francesco Paolo Russo: Center for Neurodegenerative Disease Research (CESNE), University of Padova, Padova, Italy; Department of Surgery, Oncology and Gastroenterology, Padova University Hospital, Padova, Italy
Edoardo Savarino: Center for Neurodegenerative Disease Research (CESNE), University of Padova, Padova, Italy; Department of Surgery, Oncology and Gastroenterology, Padova University Hospital, Padova, Italy
Miryam Carecchio: Parkinson and Movement Disorders Unit, Centre for Rare Neurological Diseases (ERN-RND), Department of Neuroscience, University of Padova, Padova, Italy; Center for Neurodegenerative Disease Research (CESNE), University of Padova, Padova, Italy
Elena Stocco: Department of Surgery, Oncology and Gastroenterology, Padova University Hospital, Padova, Italy; Department of Women's and Children's Health, University of Padova, Padova, Italy; Institute of Human Anatomy, Department of Neuroscience, University of Padova, Padova, Italy
Veronica Macchi: Center for Neurodegenerative Disease Research (CESNE), University of Padova, Padova, Italy; Institute of Human Anatomy, Department of Neuroscience, University of Padova, Padova, Italy; Corresponding authors at: Institute of Human Anatomy, Department of Neuroscience, University of Padova.
Raffaele De Caro: Center for Neurodegenerative Disease Research (CESNE), University of Padova, Padova, Italy; Institute of Human Anatomy, Department of Neuroscience, University of Padova, Padova, Italy
Piero Parchi: IRCCS, Istituto delle Scienze Neurologiche di Bologna (ISNB), Bologna, Italy; Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy
Luigi Bubacco: Center for Neurodegenerative Disease Research (CESNE), University of Padova, Padova, Italy; Department of Biology, University of Padova, Padova, Italy
Andrea Porzionato: Center for Neurodegenerative Disease Research (CESNE), University of Padova, Padova, Italy; Institute of Human Anatomy, Department of Neuroscience, University of Padova, Padova, Italy
Angelo Antonini: Parkinson and Movement Disorders Unit, Centre for Rare Neurological Diseases (ERN-RND), Department of Neuroscience, University of Padova, Padova, Italy; Center for Neurodegenerative Disease Research (CESNE), University of Padova, Padova, Italy; Padua Neuroscience Center (PNC), University of Padova, Padova, Italy
Aron Emmi: Parkinson and Movement Disorders Unit, Centre for Rare Neurological Diseases (ERN-RND), Department of Neuroscience, University of Padova, Padova, Italy; Center for Neurodegenerative Disease Research (CESNE), University of Padova, Padova, Italy; Institute of Human Anatomy, Department of Neuroscience, University of Padova, Padova, Italy; Padua Neuroscience Center (PNC), University of Padova, Padova, Italy; Corresponding authors at: Institute of Human Anatomy, Department of Neuroscience, University of Padova.

Journal volume & issue: Vol. 200
p. 106609

Abstract

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Background: Gastrointestinal dysfunction has emerged as a prominent early feature of Parkinson's Disease, shedding new light on the pivotal role of the enteric nervous system in its pathophysiology. However, the role of immune-cell clusters and inflammatory and glial markers in the gut pathogenetic process needs further elucidation. Objectives: We aimed to study duodenum tissue samples to characterize PD's enteric nervous system pathology further. Twenty patients with advanced PD, six with early PD, and 18 matched controls were included in the PADUA-CESNE cohort. Methods: Duodenal biopsies from 26 patients with early to advanced stage PD and 18 age-matched HCs were evaluated for the presence of surface markers (CD3+, CD4+, CD8+, CD20+, CD68+, HLA-DR), presence of misfolded alpha-synuclein and enteric glial alteration (GFAP). Correlation of immulogic pattern and clinical characteristic were analyzed. Results: The findings validate that in patients with Parkinson's Disease, the activation and reactive gliosis are linked to the neurodegeneration triggered by the presence of misfolded alpha-synuclein in the enteric nervous system. This process intensifies from the initial to the advanced stages of the disease. The clusters of T- and B-lymphocytes in the enteric system, along with the overall expression of HLA-DR in antigen-presenting cells, exceeded those in the control group. Conversely, no differences in terms of macrophage populations were found. Conclusions: These findings broaden our understanding of the mechanisms underlying the enteric nervous system's involvement in PD and point to the gastrointestinal system as a potential therapeutic target, especially in the early stages of the disease. Moreover, our results propose a role of T- and B-lymphocytes in maintaining inflammation and ultimately influencing alpha-synuclein misfolding and aggregation.

Published in Neurobiology of Disease

ISSN: 0969-9961 (Print); 1095-953X (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Medicine: Internal medicine: Neurosciences. Biological psychiatry. Neuropsychiatry
Website: https://www.journals.elsevier.com/neurobiology-of-disease

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