Deposition of Phosphorylated α-Synuclein and Activation of GSK-3β and PP2A in the PS19 Mouse Model of Tauopathy

  • Yuta Takaichi
    From the Laboratory of Veterinary Pathology, Graduate School of Agricultural and Life Sciences, The University of Tokyo , Tokyo
  • James K Chambers
    Research Laboratories for Health Science & Food Technologies and the Central Laboratories for Key Technologies, Kirin Company Ltd , Kanagawa
  • Yasuhisa Ano
    Research Laboratories for Health Science & Food Technologies and the Central Laboratories for Key Technologies, Kirin Company Ltd , Kanagawa
  • Akihiko Takashima
    Department of Life Science, Faculty of Science, Gakushuin University , Tokyo, Japan
  • Hiroyuki Nakayama
    From the Laboratory of Veterinary Pathology, Graduate School of Agricultural and Life Sciences, The University of Tokyo , Tokyo
  • Kazuyuki Uchida
    From the Laboratory of Veterinary Pathology, Graduate School of Agricultural and Life Sciences, The University of Tokyo , Tokyo

Bibliographic Information

Published
2021-06-21
Resource Type
journal article
Rights Information
  • https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model
DOI
  • 10.1093/jnen/nlab054
Publisher
Oxford University Press (OUP)

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<jats:title>Abstract</jats:title> <jats:p>The simultaneous accumulation of multiple pathological proteins, such as hyperphosphorylated tau (hp-tau) and phosphorylated α-synuclein (p-αSyn), has been reported in the brains of patients with various neurodegenerative diseases. We previously demonstrated that hp-tau-dependent p-αSyn accumulation was associated with the activation of GSK-3β in the brains of P301L tau transgenic mice. To confirm the effects of another mutant tau on p-αSyn accumulation in vivo, we herein examined the brains of PS19 mice that overexpress human P301S mutant tau. Immunohistochemically, hp-tau and p-αSyn aggregates were detected in the same neuronal cells in the cerebrum and brain stem of aged PS19 mice. A semiquantitative analysis showed a positive correlation between hp-tau and p-αSyn accumulation. Furthermore, an activated form of GSK-3β was detected within cells containing both hp-tau and p-αSyn aggregates in PS19 mice. Western blotting showed a decrease in inactivated PP2A levels in PS19 mice. The present results suggest that the overexpression of human P301S mutant tau induces p-αSyn accumulation that is accompanied by not only GSK-3β, but also PP2A activation in PS19 mice, and highlight the synergic effects between tau and αSyn in the pathophysiology of neurodegenerative diseases that show the codeposition of tau and αSyn.</jats:p>

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