Alpha-synuclein immunoreactivity and ultrastructural study of glial cytoplasmic inclusions in multiple system atrophy.
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.
Wang
Yin
Y
Institute of Neurology, Fudan University, Shanghai 200040, China. yinwang88@hotmail.com
Lü
Chuanzhen
C
Ye
Zhurong
Z
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
D009419:Nerve Tissue Proteins; C497604:SNCA protein, human; D051843:Synucleins; D051844:alpha-Synuclein