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Accumulation of phosphorylated α-synuclein in the brain and peripheral ganglia of patients with multiple system atrophy

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Abstract

We immunohistochemically examined the brain and peripheral sympathetic ganglia from eight patients with multiple system atrophy (MSA), using an antibody specific for phosphorylated α-synuclein (anti-PSer129). Phosphorylated α-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 α-synuclein in both glial and neuronal cells is a pathological feature in patients suffering from MSA.

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Acknowledgements

This work was supported in part by a Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology, Japan, and grants from The Naito Foundation of Japan, The Karoji Memorial Foundation for Medical Research, and The Uehara Memorial Foundation.

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Authors and Affiliations

  1. Department of Neuropathology, Institute of Brain Science, Hirosaki University School of Medicine, 5 Zaifu-cho, 036-8562, Hirosaki, Japan

    Makoto Nishie, Fumiaki Mori & Koichi Wakabayashi

  2. Department of Neuropathology and Neuroscience, Graduate School of Pharmaceutical Science, The University of Tokyo, Tokyo, Japan

    Hideo Fujiwara & Takeshi Iwatsubo

  3. Department of Molecular Neurobiology, Tokyo Institute of Psychiatry, Tokyo Metropolitan Organization for Medical Research, Tokyo, Japan

    Masato Hasegawa

  4. Molecular Biology Laboratory, Medicinal Research Laboratories, Taisho Pharmaceuticals, Saitama, Japan

    Makoto Yoshimoto

  5. Department of Pathology, Brain Research Institute, Niigata University, Niigata, Japan

    Hitoshi Takahashi

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  1. Makoto Nishie
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  2. Fumiaki Mori
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Correspondence to Makoto Nishie.

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Nishie, M., Mori, F., Fujiwara, H. et al. Accumulation of phosphorylated α-synuclein in the brain and peripheral ganglia of patients with multiple system atrophy. Acta Neuropathol 107, 292–298 (2004). https://doi.org/10.1007/s00401-003-0811-1

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  • DOI: https://doi.org/10.1007/s00401-003-0811-1

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