title: The underlying mechanism of prodromal PD: insights from the parasympathetic nervous system and the olfactory system.
abstract: Neurodegeneration of Parkinson's disease (PD) starts in an insidious manner, 30-50% of dopaminergic neurons have been lost in the substantia nigra before clinical diagnosis. Prodromal stage of the disease, during which the disease pathology has started but is insufficient to result in clinical manifestations, offers a valuable window for disease-modifying therapies. The most focused underlying mechanisms linking the pathological pattern and clinical characteristics of prodromal PD are the prion hypothesis of alpha-synuclein and the selective vulnerability of neurons. In this review, we consider the two potential portals, the vagus nerve and the olfactory bulb, through which abnormal alpha-synuclein can access the brain. We review the clinical, pathological and neuroimaging evidence of the parasympathetic nervous system and the olfactory system in the neurodegenerative process and using the two systems as models to discuss the internal homogeneity and heterogeneity of the prodromal stage of PD, including both the clustering and subtyping of symptoms and signs. Finally, we offer some suggestions on future directions for imaging studies in prodromal Parkinson's disease.
authors.affiliation: Department of Neurobiology, Neurology and Geriatrics, Xuanwu Hospital Capital Medical University, Beijing, 100051 China.|Beijing Key Laboratory on Parkinson's Disease, Parkinson Disease Center of Beijing Institute for Brain Disorders, Beijing, 100051 China.|Pacific Parkinson's Research Centre, Division of Neurology and Djavad Mowafaghian Centre for Brain Health, University of British Columbia and Vancouver Coastal Health, Vancouver, V6T 1Z3 BC Canada.
authors.forename: Shu-Ying
authors.initials: SY
authors.lastname: Liu
authors.affiliation: Department of Neurobiology, Neurology and Geriatrics, Xuanwu Hospital Capital Medical University, Beijing, 100051 China.|Beijing Key Laboratory on Parkinson's Disease, Parkinson Disease Center of Beijing Institute for Brain Disorders, Beijing, 100051 China.
authors.forename: Piu
authors.initials: P
authors.lastname: Chan
authors.affiliation: Pacific Parkinson's Research Centre, Division of Neurology and Djavad Mowafaghian Centre for Brain Health, University of British Columbia and Vancouver Coastal Health, Vancouver, V6T 1Z3 BC Canada.
authors.forename: A Jon
authors.initials: AJ
authors.lastname: Stoessl
keywords: Alpha-synuclein; Olfactory system; Parasympathetic nervous system; Parkinson’s disease; Prodromal; Subtype