Sympathetic and parasympathetic subtypes of body-first Lewy body disease observed in postmortem tissue from prediagnostic individuals

Andersen, Katrine B.; Krishnamurthy, A.; Just, Mie Kristine; Berge, Nathalie Van Den; Skjærbæk, Casper; Horsager, Jacob; Knudsen, Karoline; Vogel, Jacob W.; Toledo, Jon B.; Attems, Johannes; Polvikoski, Tuomo; Saito, Yuko; Murayama, Shigeo; Borghammer, Per

doi:10.1038/s41593-025-01910-9

articleNature NeuroscienceMar 13, 2025HYBRID OA

Sympathetic and parasympathetic subtypes of body-first Lewy body disease observed in postmortem tissue from prediagnostic individuals

KBKatrine B. Andersen AKA. Krishnamurthy MKMie Kristine Just NVNathalie Van Den Berge CSCasper Skjærbæk

Aarhus University · Aarhus University Hospital · +8 more institutions

PubMed

Indexed incrossrefpubmed

Abstract

Recent studies suggest the existence of brain-first and body-first subtypes within the Lewy body disorder (LBD) spectrum, including Parkinson's disease. These studies primarily focused on α-synuclein propagation through the parasympathetic vagal and olfactory bulb routes, leaving the possibility of a sympathetic nervous system spreading route unexplored. In the present study, we analyzed two postmortem datasets, which included 173 and 129 cases positive for Lewy pathology. We observed a clear distinction between brain-first and body-first subtypes in early prediagnostic cases with mild Lewy pathology. Brain-first cases displayed minimal peripheral organ pathology in prediagnostic phases, contrasting with…

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Keywords

Lewy body
Autonomic nervous system
Parasympathetic nervous system
Lewy body disease
Alpha-synuclein
Neuroscience
Sympathetic nervous system
Pathology

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