Glial cytoplasmic inclusions in white matter oligodendrocytes of multiple system atrophy brains contain insoluble α-synuclein

Pang Hsien Tu, James E. Galvin, Minami Baba, Benoit Giasson, Taisuke Tomita, Susan Leight, Shigeo Nakajo, Takeshi Iwatsubo, John Q. Trojanowski, Virginia M.Y. Lee

Research output: Contribution to journalArticlepeer-review

552 Scopus citations

Abstract

Recently, α-synuclein was shown to be a structural component of the filaments in Lewy bodies (LBs) of Parkinson's disease (PD), dementia with LBs (DLB) as well as the LB variant of Alzheimer's disease, and this suggests that α-synuclein could play a mechanistic role in the pathogenesis of these disorders. To determine whether α-synuclein is a building block of inclusions in other neurodegenerative movement disorders, we examined brains from patients with multiple system atrophy (MSA) and detected α-synuclein, but not β- or γ-synuclein, in glial cytoplasmic inclusions (GCIs) throughout the MSA brain. In MSA white matter, α-synuclein-positive GCIs were restricted to oligodendrocytes, and α-synuclein was localized to the filaments in GCIs by immunoelectron microscopy. Finally, we demonstrated that insoluble α-synuclein accumulated selectively in MSA white matter with α- synuclein-positive GCIs. Taken together with evidence that LBs contain insoluble α-synuclein, our data suggest that a reduction in the solubility of α-synuclein may induce this protein to form filaments that aggregate into cytoplasmic inclusions, which contribute to the dysfunction or death of glial cells as well as neurons in neurodegenerative disorders with different phenotypes.

Original languageEnglish (US)
Pages (from-to)415-422
Number of pages8
JournalAnnals of neurology
Volume44
Issue number3
DOIs
StatePublished - Sep 1998
Externally publishedYes

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

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