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Lookup NU author(s): Dr Emma Lethbridge, Professor David BrooksORCiD
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
Parkinson’s disease (PD) is the fastest growing neurodegenerative disorder in the world and much of its pathophysiological and clinical advance has been based on research addressing motor symptomatology and phenotypes. A range of clinical data-driven and phenotypic studies supported by extensive neuropathological and in vivo neuroimaging data suggest the existence of distinct non-motor endophenotypes even at diagnosis, a concept further strengthened by the predominant non-motor spectrum of prodromal PD. Preclinical and clinical studies support the early dysfunction of noradrenergic transmission in the central and the peripheral nervous system circuits in PD resulting in the expression of a specific cluster of non-motor symptoms (NMS) underpinned by rapid eye movement (REM) behaviour disorder, pain, dysautonomia with orthostatic hypotension as well as urinary dysfunction, and anxiety among others. Cluster analyses of large independent cohorts of patients with PD and phenotypic-focused studies confirm a noradrenergic subtype as has been previously postulated but not specifically characterised. Here, we discuss the translational approaches that have unravelled the clinical and neuropathological processes which underpin the noradrenergic PD subtype. Although some overlap with other potential subtypes is inevitable as PD progresses, we reflect on the considerable advance towards modern and bespoke personalised medicine delivery for the noradrenergic PD.
Author(s): Chaudhuri KR, Leta V, Bannister K, Brooks DJ, Svenningsson P
Publication type: Review
Publication status: Published
Journal: Nature Reviews Neurology
Year: 2023
Volume: 19
Pages: 333-345
Print publication date: 01/06/2023
Online publication date: 04/05/2023
Acceptance date: 16/03/2023
ISSN (print): 1759-4758
ISSN (electronic): 1759-4766
URL: https://doi.org/10.1038/s41582-023-00802-5
DOI: 10.1038/s41582-023-00802-5
ePrints DOI: 10.57711/eknk-mx60
