Browse by author
Lookup NU author(s): Lina Patterson, Professor Stephen Rushton, Professor Johannes Attems, Professor Alan ThomasORCiD, Dr Christopher Morris
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND).
© 2018 The Authors Brain Pathology published by John Wiley & Sons Ltd on behalf of International Society of Neuropathology Aims: Depression is commonly observed even in prodromal stages of Lewy body disorders (LBD), and is associated with cognitive impairment and a faster rate of cognitive decline. Given the role of dopamine in the development of movement disorders, but also in motivation and reward, we investigated neurodegenerative pathology in dopaminergic circuitry in Parkinson’s disease (PD), PD with dementia (PDD) and dementia with Lewy bodies (DLB) patients in relation to depressive symptoms. Methods: α-synuclein, hyperphosphorylated tau and amyloid-beta pathology was assessed in 17 DLB, 14 PDD and 8 PD cases within striatal and midbrain subregions, with neuronal cell density assessed in substantia nigra and ventral tegmental area. Additionally, we used a structural equation modeling (SEM) approach to investigate the extent to which brain connectivity might influence the deposition of pathological proteins within dopaminergic pathways. Results: A significantly higher α-synuclein burden was observed in the substantia nigra (P = 0.006), ventral tegmental area (P = 0.011) and nucleus accumbens (P = 0.031) in LBD patients with depression. Significant negative correlations were observed between cell density in substantia nigra with Lewy body (LB) Braak stage (P = 0.013), whereas cell density in ventral tegmental area showed negative correlations with LB Braak stage (P = 0.026) and neurofibrillary tangle Braak stage (P = 0.007). Conclusions: Dopaminergic α-synuclein pathology appears to drive depression. Selective targeting of dopaminergic pathways may therefore provide symptomatic relief for depressive symptoms in LBD patients.
Author(s): Patterson L, Rushton SP, Attems J, Thomas AJ, Morris CM
Publication type: Article
Publication status: Published
Journal: Brain Pathology
Year: 2019
Volume: 29
Issue: 4
Pages: 544-557
Print publication date: 01/07/2019
Online publication date: 24/12/2018
Acceptance date: 06/12/2018
Date deposited: 15/02/2019
ISSN (print): 1015-6305
ISSN (electronic): 1750-3639
Publisher: Wiley-Blackwell
URL: https://doi.org/10.1111/bpa.12697
DOI: 10.1111/bpa.12697
Altmetrics provided by Altmetric
