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Wake and non-rapid eye movement sleep dysfunction is associated with colonic neuropathology in Parkinson’s disease

medRxiv
2023
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Wake and non-rapid eye movement sleep dysfunction is associated with colonic neuropathology in Parkinson's disease

2023 OCT 18 (NewsRx) -- By a News Reporter-Staff News Editor at Health & Medicine Daily -- According to news reporting based on a preprint

Article Description

Study Objectives: The body-first Parkinson’s disease (PD) hypothesis suggests initial gut Lewy body pathology that propagates to the pons before reaching the substantia nigra, and subsequently progresses to the diencephalic and cortical levels. This disease course may also be the most likely in PD with rapid eye movement sleep behavior disorder (RBD). Objectives: We aimed to explore the potential association between colonic phosphorylated alpha-synuclein histopathology (PASH) and diencephalic or cortical dysfunction evidenced by non-rapid eye movement (NREM) sleep and wakefulness polysomnographic markers. Methods: In a study involving 43 patients with PD who underwent clinical examination, rectosigmoidoscopy, and polysomnography, we detected PASH on colonic biopsies using whole-mount immunostaining. We performed a visual semi-quantitative and automated quantification of spindle and slow wave features of NREM sleep, and the wake dominant frequency, and then determined Braak and Arizona stage classifications for PD severity based on sleep and wake electroencephalographic features. Results: The visual analysis aligned with the automated quantified spindle characteristics and the wake dominant frequency. Altered NREM sleep and wake parameters correlated with markers of PD severity, colonic PASH, and RBD diagnosis. Colonic PASH frequency also increased in parallel to presumed PD Braak and Arizona stage classifications. Conclusions: Colonic PASH in PD is strongly associated with widespread brain sleep and wake dysfunction, pointing toward likely extensive diffusion of the pathological process in the presumptive body-first PD phenotype. Visual and automated analyses of polysomnography signals provide useful markers to gauge covert brain dysfunction in PD.

Bibliographic Details

Sadoc, Mathilde; Clairembault, Thomas; Coron, Emmanuel; Berthomier, Christian; Le Dily, Séverine; Vavasseur, Fabienne; Pavageau, Albane; St Louis, Erik K; Péréon, Yann; Neunlist, Michel; Derkinderen, Pascal; Leclair-Visonneau, Laurène

Cold Spring Harbor Laboratory

Medicine

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