title: Accumulation of phosphorylated alpha-synuclein in the brain and peripheral ganglia of patients with multiple system atrophy.
abstract: We immunohistochemically examined the brain and peripheral sympathetic ganglia from eight patients with multiple system atrophy (MSA), using an antibody specific for phosphorylated alpha-synuclein (anti-PSer129). Phosphorylated alpha-synuclein was deposited in five cellular locations: oligodendroglial cytoplasm and nucleus, and neuronal cytoplasm, processes and nucleus. Many neuronal cytoplasmic inclusions (NCIs) were found in the pontine and inferior olivary nuclei and, to a lesser extent, in the substantia nigra, locus ceruleus, and neocortical and hippocampal neurons. NCIs were also found in the sympathetic ganglia in two out of the eight cases. Moreover, anti-PSer129 immunohistochemistry revealed extensive neuropil pathology; swollen neurites were abundant in the pontine nucleus, delicate neurites were observed in the deeper layers of the cerebral cortex and thalamus, and neuropil threads and dot-like structures were distributed in the basal ganglia and brainstem. Diffuse neuronal cytoplasmic staining (pre-NCI) was frequently found in the pontine and inferior olivary nuclei. Thus, the widespread accumulation of phosphorylated alpha-synuclein in both glial and neuronal cells is a pathological feature in patients suffering from MSA.
authors.affiliation: Department of Neuropathology, Institute of Brain Science, Hirosaki University School of Medicine, 5 Zaifu-cho, 036-8562, Hirosaki, Japan. nishie@cc.hirosaki-u.ac.jp
authors.forename: Makoto
authors.initials: M
authors.lastname: Nishie
authors.forename: Fumiaki
authors.initials: F
authors.lastname: Mori
authors.forename: Hideo
authors.initials: H
authors.lastname: Fujiwara
authors.forename: Masato
authors.initials: M
authors.lastname: Hasegawa
authors.forename: Makoto
authors.initials: M
authors.lastname: Yoshimoto
authors.forename: Takeshi
authors.initials: T
authors.lastname: Iwatsubo
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Takahashi
authors.forename: Koichi
authors.initials: K
authors.lastname: Wakabayashi
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D002452:Cell Count / Q000379:methods; D022082:Cellular Structures / Q000378:metabolism / Q000473:pathology; D005728:Ganglia, Sympathetic / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D002479:Inclusion Bodies / Q000378:metabolism / Q000473:pathology; D016631:Lewy Bodies / Q000378:metabolism / Q000473:pathology; D020961:Lewy Body Disease / Q000378:metabolism / Q000473:pathology; D008875:Middle Aged; D019578:Multiple System Atrophy / Q000378:metabolism* / Q000473:pathology; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009474:Neurons / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D010300:Parkinson Disease / Q000378:metabolism / Q000473:pathology; D011180:Postmortem Changes; D013194:Staining and Labeling / Q000379:methods; D051843:Synucleins; D051844:alpha-Synuclein
chemical_list: D009419:Nerve Tissue Proteins; C497604:SNCA protein, human; D051843:Synucleins; D051844:alpha-Synuclein