Luminescent conjugated oligothiophenes distinguish between α-synuclein assemblies of Parkinson’s disease and multiple system atrophy
Authors
Klingstedt, Therése
Ghetti, Bernardino
Holton, Janice L.
Ling, Helen
Nilsson, K. Peter R.
Goedert, Michel
Publication Date
2019-12-03Journal Title
Acta Neuropathologica Communications
Publisher
BioMed Central
Volume
7
Issue
1
Language
en
Type
Article
This Version
VoR
Metadata
Show full item recordCitation
Klingstedt, T., Ghetti, B., Holton, J. L., Ling, H., Nilsson, K. P. R., & Goedert, M. (2019). Luminescent conjugated oligothiophenes distinguish between α-synuclein assemblies of Parkinson’s disease and multiple system atrophy. Acta Neuropathologica Communications, 7 (1)https://doi.org/10.1186/s40478-019-0840-1
Abstract
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.
Keywords
Research, α-Synuclein, Luminescent conjugated oligothiophene, Multiple system atrophy, Neurodegeneration, Parkinson’s disease, Spectral analysis
Sponsorship
Fondation pour la Recherche sur Alzheimer (N/A)
UK Medical Research Council (MC_U105184291)
Vetenskapsrådet (2016-00748)
National Institute on Aging (PHS P30 AG010133)
Multiple System Atrophy Trust (N/A, N/A)
Multiple System Atrophy Coalition (N/A)
Fund Sophia managed by the King Baudouin Foundation (N/A, N/A)
CBD Solutions (512385)
Identifiers
s40478-019-0840-1, 840
External DOI: https://doi.org/10.1186/s40478-019-0840-1
This record's URL: https://www.repository.cam.ac.uk/handle/1810/313910
Rights
Licence:
http://creativecommons.org/licenses/by/4.0/