Gut-Initiated Alpha Synuclein Fibrils Drive Parkinson's Disease Phenotypes: Temporal Mapping of non-Motor Symptoms and REM Sleep Behavior Disorder.

Publication Type	Preprint
Authors	Dautan D, Paslawski W, Montejo S, Doyon D, Marangiu R, Kaplitt M, Chen R, Dawson V, Zhang X, Dawson T, Svenningsson P
Journal	bioRxiv
Date Published	04/26/2024
ISSN	2692-8205
Abstract	Parkinson's disease (PD) is characterized by progressive motor as well as less recognized non-motor symptoms that arise often years before motor manifestation, including sleep and gastrointestinal disturbances. Despite the heavy burden on the patient's quality of life, these non-motor manifestations are poorly understood. To elucidate the temporal dynamics of the disease, we employed a mouse model involving injection of alpha-synuclein (αSyn) pre-formed fibrils (PFF) in the duodenum and antrum as a gut-brain model of Parkinsonism. Using anatomical mapping of αSyn-PFF propagation and behavioral and physiological characterizations, we unveil a correlation between post-injection time the temporal dynamics of αSyn propagation and non-motor/motor manifestations of the disease. We highlight the concurrent presence of αSyn aggregates in key brain regions, expressing acetylcholine or dopamine, involved in sleep duration, wakefulness, and particularly REM-associated atonia corresponding to REM behavioral disorder-like symptoms. This study presents a novel and in-depth exploration into the multifaceted nature of PD, unraveling the complex connections between α-synucleinopathies, gut-brain connectivity, and the emergence of non-motor phenotypes.
DOI	10.1101/2024.04.22.590542
PubMed ID	38712208
PubMed Central ID	PMC11071367