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

• Published in: Acta neuropathologica communications Vol. 7; no. 1; p. 193
• Main Authors: Klingstedt, Therése, Ghetti, Bernardino, Holton, Janice L, Ling, Helen, Nilsson, K Peter R, Goedert, Michel
• Format: Journal Article
• Language: English
• Published: England BioMed Central 03.12.2019; BMC
• Subjects: Aged; Aged, 80 and over; alpha-Synuclein - analysis; alpha-Synuclein - metabolism; Atrophy; Brain; Dementia; Diagnosis, Differential; Disease; Ethanol; Female; Fluorescent Dyes - analysis; Fluorescent Dyes - metabolism; Humans; Labeling; Laboratories; Ligands; Luminescent conjugated oligothiophene; Luminescent Measurements - methods; Male; Middle Aged; Multiple system atrophy; Multiple System Atrophy - metabolism; Multiple System Atrophy - pathology; Neurodegeneration; Optical Imaging - methods; Parkinson Disease - metabolism; Parkinson Disease - pathology; Parkinson's disease; Spectral analysis; Thiophenes - analysis; Thiophenes - metabolism; α-Synuclein; Multiple system atrophy; Luminescent conjugated oligothiophene; α-Synuclein; Neurodegeneration; Parkinson’s disease; Spectral analysis; alpha-Synuclein; Parkinsons disease
• ISSN: 2051-5960; 2051-5960
• DOI: 10.1186/s40478-019-0840-1

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.