title: Filamentous aggregations of phosphorylated α-synuclein in Schwann cells (Schwann cell cytoplasmic inclusions) in multiple system atrophy.
abstract: BACKGROUND
  The histological hallmark of multiple system atrophy (MSA) is the presence of filamentous aggregations of phosphorylated α-synuclein in oligodendrocytes, referred to as glial cytoplasmic inclusions (GCIs). Although GCIs can occur widely in the central nervous system, accumulation of phosphorylated α-synuclein in Schwann cells has not been reported in MSA. We immunohistochemically examined the cranial and spinal nerves, peripheral ganglia and visceral autonomic nervous system of patients with MSA (n = 14) and control subjects (n = 20).
  
  
  RESULTS
  In MSA, accumulation of phosphorylated α-synuclein was found in the cytoplasm of Schwann cells. These Schwann cell cytoplasmic inclusions (SCCIs) were also immunopositive for ubiquitin and p62. SCCIs were found in 12 of 14 patients with MSA (85.7 %). They were most frequent in the anterior nerve of the sacral cord and, to a lesser extent, in the cranial nerves (oculomotor, glossopharyngeal-vagus and hypoglossal nerves), and spinal and sympathetic ganglia. SCCIs were rarely found in the visceral organs. Immunoelectron microscopy demonstrated that the SCCIs consisted of abnormal filaments, 15-20 nm in diameter. No such inclusions were found in controls.
  
  
  CONCLUSIONS
  The present findings indicate that Schwann cells are also involved in the disease process of MSA.
authors.affiliation: Department of Neuropathology, Institute of Brain Science, Hirosaki University Graduate School of Medicine, 5 Zaifu-cho, Hirosaki, 036-8562, Japan. k-nkmr@med.kanazawa-u.ac.jp.|Department of Neurology and Neurobiology of Ageing, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan. k-nkmr@med.kanazawa-u.ac.jp.
authors.forename: Keiko
authors.initials: K
authors.lastname: Nakamura
authors.affiliation: Department of Neuropathology, Institute of Brain Science, Hirosaki University Graduate School of Medicine, 5 Zaifu-cho, Hirosaki, 036-8562, Japan. neuropal@hirosaki-u.ac.jp.
authors.forename: Fumiaki
authors.initials: F
authors.lastname: Mori
authors.affiliation: Department of Neurology, Aomori Prefectural Central Hospital, Aomori, Japan. t-kon@umin.ac.jp.
authors.forename: Tomoya
authors.initials: T
authors.lastname: Kon
authors.affiliation: Department of Neuropathology, Institute of Brain Science, Hirosaki University Graduate School of Medicine, 5 Zaifu-cho, Hirosaki, 036-8562, Japan. kunikazutanji@hotmail.com.
authors.forename: Kunikazu
authors.initials: K
authors.lastname: Tanji
authors.affiliation: Department of Neuropathology, Institute of Brain Science, Hirosaki University Graduate School of Medicine, 5 Zaifu-cho, Hirosaki, 036-8562, Japan. yasuomiki@hotmail.com.
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Miki
authors.affiliation: Department of Neurology, Aomori Prefectural Central Hospital, Aomori, Japan. masahiko_tomiyama@med.pref.aomori.jp.
authors.forename: Masahiko
authors.initials: M
authors.lastname: Tomiyama
authors.affiliation: Department of Pathology, Aomori Prefectural Central Hospital, Aomori, Japan. hidekachi_kurotaki@med.pref.aomori.jp.
authors.forename: Hidekachi
authors.initials: H
authors.lastname: Kurotaki
authors.affiliation: Department of Pathology, Brain Research Institute, University of Niigata, Niigata, Japan. yasuko@bri.niigata-u.ac.jp.
authors.forename: Yasuko
authors.initials: Y
authors.lastname: Toyoshima
authors.affiliation: Department of Pathological Neuroscience, Center for Bioresource-based Researches, Brain Research Institute, University of Niigata, Niigata, Japan. kakita@bri.niigata-u.ac.jp.
authors.forename: Akiyoshi
authors.initials: A
authors.lastname: Kakita
authors.affiliation: Department of Pathology, Brain Research Institute, University of Niigata, Niigata, Japan. hitoshi@bri.niigata-u.ac.jp.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Takahashi
authors.affiliation: Department of Neurology and Neurobiology of Ageing, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan. m-yamada@med.kanazawa-u.ac.jp.
authors.forename: Masahito
authors.initials: M
authors.lastname: Yamada
authors.affiliation: Department of Neuropathology, Institute of Brain Science, Hirosaki University Graduate School of Medicine, 5 Zaifu-cho, Hirosaki, 036-8562, Japan. koichi@hirosaki-u.ac.jp.
authors.forename: Koichi
authors.initials: K
authors.lastname: Wakabayashi
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000368:Aged; D001341:Autonomic Nervous System / Q000473:pathology; D003391:Cranial Nerves / Q000473:pathology; D003599:Cytoskeleton / Q000473:pathology* / Q000648:ultrastructure; D005260:Female; D005724:Ganglia / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D002479:Inclusion Bodies / Q000473:pathology* / Q000648:ultrastructure; D008297:Male; D016253:Microscopy, Immunoelectron; D008875:Middle Aged; D019578:Multiple System Atrophy / Q000378:metabolism* / Q000473:pathology*; D010766:Phosphorylation; D012583:Schwann Cells / Q000166:cytology / Q000378:metabolism / Q000473:pathology*; D000071456:Sequestosome-1 Protein; D013127:Spinal Nerves / Q000473:pathology; D025801:Ubiquitin / Q000378:metabolism; D051844:alpha-Synuclein / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C099718:SQSTM1 protein, human; D000071456:Sequestosome-1 Protein; D025801:Ubiquitin; D051844:alpha-Synuclein