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Open Access 01-03-2019 | Parkinson's Disease | Original Paper

Wide distribution of alpha-synuclein oligomers in multiple system atrophy brain detected by proximity ligation

Authors: Hiroaki Sekiya, Hisatomo Kowa, Hinako Koga, Mariko Takata, Wataru Satake, Naonobu Futamura, Itaru Funakawa, Kenji Jinnai, Motonori Takahashi, Takeshi Kondo, Yasuhiro Ueno, Motoi Kanagawa, Kazuhiro Kobayashi, Tatsushi Toda

Published in: Acta Neuropathologica | Issue 3/2019

Abstract

Multiple system atrophy (MSA) is a fatal adult-onset neurodegenerative disease that is characterized by varying degrees of cerebellar dysfunction and Parkinsonism. The neuropathological hallmark of MSA is alpha-synuclein (AS)-positive glial cytoplasmic inclusions (GCIs). Although severe neuronal loss (NL) is also observed in MSA, neuronal inclusions (NIs) are rare compared to GCIs, such that the pathological mechanism of NL in MSA is unclear. GCIs and NIs are late-stage pathology features relative to AS oligomers and may not represent early pathological changes in MSA. To reveal the early pathology of MSA, it is necessary to examine the early aggregation of AS, i.e., AS oligomers. Here, we adopted a proximity ligation assay (PLA) to examine the distribution of AS oligomers in brain tissue samples from patients with MSA and other diseases. Surprisingly, MSA brains showed a widespread distribution and abundant accumulation of oligomeric AS in neurons as well as oligodendrocytes of the neocortex. In several regions, oligomeric AS signal intensity was higher in cases with MSA than in cases with Parkinson’s disease. In contrast to previous studies, AS–PLA revealed abundant AS oligomer accumulation in Purkinje cells in MSA brains, identifying oligomeric AS accumulation as a possible cause of Purkinje cell loss. This wide distribution of AS oligomers in MSA brain neurons has not been described previously and indicates a pathological mechanism of NL in MSA.

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Title: Wide distribution of alpha-synuclein oligomers in multiple system atrophy brain detected by proximity ligation
Authors: Hiroaki Sekiya
Hisatomo Kowa
Hinako Koga
Mariko Takata
Wataru Satake
Naonobu Futamura
Itaru Funakawa
Kenji Jinnai
Motonori Takahashi
Takeshi Kondo
Yasuhiro Ueno
Motoi Kanagawa
Kazuhiro Kobayashi
Tatsushi Toda
Publication date: 01-03-2019
Publisher: Springer Berlin Heidelberg
Keyword: Parkinson's Disease
Published in: Acta Neuropathologica / Issue 3/2019
Print ISSN: 0001-6322
Electronic ISSN: 1432-0533
DOI: https://doi.org/10.1007/s00401-019-01961-w

At a glance: The STEP trials

Springer Medicine

Wide distribution of alpha-synuclein oligomers in multiple system atrophy brain detected by proximity ligation

Abstract

At a glance: The STEP trials

Springer Medicine

Abstract

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