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Luminescent conjugated oligothiophenes distinguish between α-synuclein assemblies of Parkinson's disease and multiple system atrophy

Klingstedt, T; Ghetti, B; Holton, JL; Ling, H; Nilsson, KPR; Goedert, M; (2019) Luminescent conjugated oligothiophenes distinguish between α-synuclein assemblies of Parkinson's disease and multiple system atrophy. Acta Neuropathologica Communications , 7 , Article 193. 10.1186/s40478-019-0840-1. Green open access

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Abstract

Synucleinopathies [Parkinson’s disease with or without dementia, dementia with Lewy bodies and multiple system atrophy] are neurodegenerative diseases that are defined by the presence of filamentous α-synuclein inclusions. We investigated the ability of luminescent conjugated oligothiophenes to stain the inclusions of Parkinson’s disease and multiple system atrophy. They stained the Lewy pathology of Parkinson’s disease and the glial cytoplasmic inclusions of multiple system atrophy. Spectral analysis of HS-68-stained inclusions showed a red shift in multiple system atrophy, but the difference with Parkinson’s disease was not significant. However, when inclusions were double-labelled for HS-68 and an antibody specific for α-synuclein phosphorylated at S129, they could be distinguished based on colour shifts with blue designated for Parkinson’s disease and red for multiple system atrophy. The inclusions of Parkinson’s disease and multiple system atrophy could also be distinguished using fluorescence lifetime imaging. These findings are consistent with the presence of distinct conformers of assembled α-synuclein in Parkinson’s disease and multiple system atrophy.

Type: Article
Title: Luminescent conjugated oligothiophenes distinguish between α-synuclein assemblies of Parkinson's disease and multiple system atrophy
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.1186/s40478-019-0840-1
Publisher version: https://doi.org10.1186/s40478-019-0840-1
Language: English
Additional information: This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
Keywords: α-Synuclein, Luminescent conjugated oligothiophene, Multiple system atrophy, Neurodegeneration, Parkinson’s disease, Spectral analysis
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Clinical and Movement Neurosciences
URI: https://discovery.ucl.ac.uk/id/eprint/10088303
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