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

Published version
Peer-reviewed

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Article

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Authors

Klingstedt, Therése 
Ghetti, Bernardino 
Holton, Janice L 
Ling, Helen 
Nilsson, K Peter R 

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.

Description

Keywords

Luminescent conjugated oligothiophene, Multiple system atrophy, Neurodegeneration, Parkinson’s disease, Spectral analysis, α-Synuclein, Aged, Aged, 80 and over, Diagnosis, Differential, Female, Fluorescent Dyes, Humans, Luminescent Measurements, Male, Middle Aged, Multiple System Atrophy, Optical Imaging, Parkinson Disease, Thiophenes, alpha-Synuclein

Journal Title

Acta Neuropathol Commun

Conference Name

Journal ISSN

2051-5960
2051-5960

Volume Title

7

Publisher

Springer Science and Business Media LLC
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)