title: Alpha-synuclein immunoreactivity and ultrastructural study of glial cytoplasmic inclusions in multiple system atrophy.
abstract: OBJECTIVE
  To understand the possible pathogenesis of sporadic multiple system atrophy (MSA).
  
  
  METHODS
  The immunoreactivity and ultrastructural features of glial cytoplasmic inclusions (GCIs) in 12 autopsy patients with MSA and 4 normal control groups were studied. All regional sections from each subject were evaluated with HE staining, Klüver-Barrera (KB), Holzer's, modified Gallyas-Braak's (GB) methods and immunohistochemical staining with alpha-synuclein and ubiquitin antibodies. Pontine white matter with abundant GCIs from case 1 was examined, using conventional electron microscopy, Gallyas-Braak's electron microscopy and immunoelectron microscopy.
  
  
  RESULTS
  The presence of GCIs as constantly demonstrated in all MSA patients. Strong alpha-synuclein immunoreactivity was observed in all of the ubiquitinated GCIs. However, the density of alpha-synuclein positive GCIs differed from case to case, and there was no relationship between the density of GCIs and age, sex, or MSA subtype. Ultrastructural features indicated that argyrophilic granule-associated filaments of about 25 nm in diameter were the predominant constituents of GCIs, and the anti alpha-synuclein antibody selectively labeled in these filaments. No GCIs and alpha-synuclein immunoreaction were found in control brain tissues.
  
  
  CONCLUSIONS
  GCI was a pathognomonic change in sporadic MSA patients. Accumulation of alpha-synuclein in GCIs may occur during the early stags of MSA. Seletcive alpha-synuclein positive abnormal microtubules in GCIs therefore play an important role in the pathogenesis of MSA.
authors.affiliation: Institute of Neurology, Fudan University, Shanghai 200040, China. yinwang88@hotmail.com
authors.forename: Yin
authors.initials: Y
authors.lastname: Wang
authors.forename: Chuanzhen
authors.initials: C
authors.lastname: Lü
authors.forename: Zhurong
authors.initials: Z
authors.lastname: Ye
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D002479:Inclusion Bodies / Q000648:ultrastructure*; D008297:Male; D016253:Microscopy, Immunoelectron; D008875:Middle Aged; D019578:Multiple System Atrophy / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D009419:Nerve Tissue Proteins / Q000032:analysis*; D009457:Neuroglia / Q000648:ultrastructure*; D051843:Synucleins; D051844:alpha-Synuclein
chemical_list: D009419:Nerve Tissue Proteins; C497604:SNCA protein, human; D051843:Synucleins; D051844:alpha-Synuclein