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Published on: November 28, 2025
REM sleep behavior disorder is related to enteric neuropathology in Parkinson disease
Laurène Leclair-Visonneau1, Thomas Clairembault2, Emmanuel Coron2
1From Inserm (L.L.-V., T.C., E.C., M.N., P.D.), U1235, Nantes; University Nantes (L.L.-V., T.C., E.C., Y.P., M.N., P.D.); Inserm (L.L.-V., E.C., S.L.D., F.V., P.D.), CIC-04; CHU Nantes (L.L.-V., Y.P.), Department of Clinical Neurophysiology; CHU Nantes (T.C., E.C., F.V., M.N.), Institut des Maladies de l'Appareil Digestif; CHU Nantes (M.D.), Plateforme de Biométrie, Département Promotion DRCI; and CHU Nantes (P.D.), Department of Neurology, France. laurene.leclair@chu-nantes.fr.
Objective:
To determine whether REM sleep behavior disorder (RBD) in Parkinson disease (PD) is associated with lesions and dysfunctions of the autonomic nervous system by evaluating enteric phosphorylated α-synuclein histopathology (PASH) and permeability.
Methods:
A total of 45 patients with PD were included in this cross-sectional study. RBD was diagnosed on the basis of a standardized clinical interview and confirmed by polysomnography. For each patient, 5 biopsies were taken at the junction between the sigmoid and descending colon during the course of a rectosigmoidoscopy. For the detection of enteric PASH, 2 colonic biopsies were analyzed by immunohistochemistry with antibodies against phosphorylated α-synuclein and PGP9.5 in 43 patients (2 patients were excluded because only 1 biopsy was available). The paracellular permeability and transcellular permeability were evaluated by measuring sulfonic acid and horseradish peroxidase flux, respectively, in the 3 remaining biopsies mounted in Ussing chambers.
Results:
Enteric PASH was more frequent in the subgroup of patients with PD with RBD compared to patients without RBD (18 of 28, 64.3%, vs 2 of 15, 13.3%, respectively, p < 0.01). No differences were observed in intestinal permeability between patients with PD with and without RBD.
Conclusions:
Patients with PD and RBD have a greater frequency of synuclein pathology in the enteric nervous system, suggesting that RBD is associated with widespread synuclein neuropathology.
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