Amyloid β accelerates phosphorylation of tau and neurofibrillary tangle formation in an amyloid precursor protein and tau double-transgenic mouse model

Yusuke Seino, Takeshi Kawarabayashi, Yasuhito Wakasaya, Mitsunori Watanabe, Ayumi Takamura, Yukiko Yamamoto-Watanabe, Tomoko Kurata, Koji Abe, Masaki Ikeda, David Westaway, Tetsuro Murakami, Peter St George Hyslop, Etsuro Matsubara, Mikio Shoji

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

In Alzheimer's disease, Aβ deposits are considered the initial cardinal events that induce tauopathy secondarily. However, the relationship between Aβ amyloidosis and tauopathy has not been determined in detail. We produced double transgenic mice, 2×TgTau+/-APP+/-, by mating Tg2576 mice that exhibit Aβ amyloidosis and TgTauP301L mice that show tauopathy, and statistically analyzed the effect of Aβ accumulation on tauopathy. There was no significant difference in theprogression of Aβ accumulation among 2×TgTau+/-APP+/- and 1×TgTau-/-APP+/-, and tau accumulation among 2×TgTau+/-APP+/- and 1×Tg Tau+/-APP-/-. The appearance rates of phosphorylated tau developing in neurons and processes were significantly accelerated in 2×TgTau+/-APP+/- mice compared with those in 1×TgTau+/-APP-/- mice at 23 months of age. Accumulation of phosphorylated and confomationally altered tau and GSK3β in neuronal processes was accelerated in the white matter in 2×TgTau+/-APP+/-. The level of phosphorylated tau in the sarkosyl-insoluble fraction was increased in 2×TgTau+/-APP+/- brains compared with that in 1×TgTau+/-APP-/- brains. Thus, Aβ amyloid partially enhances tauopathy through accumulation of insoluble, phosphorylated, and conformationally changed tau in neuronal cytoplasm and processes in the late stage.

Original languageEnglish
Pages (from-to)3547-3554
Number of pages8
JournalJournal of Neuroscience Research
Volume88
Issue number16
DOIs
Publication statusPublished - Dec 2010

Keywords

  • Alzheimer's disease
  • Double transgenic mouse
  • Neurofibrillary tangles

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience

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  • Cite this

    Seino, Y., Kawarabayashi, T., Wakasaya, Y., Watanabe, M., Takamura, A., Yamamoto-Watanabe, Y., Kurata, T., Abe, K., Ikeda, M., Westaway, D., Murakami, T., Hyslop, P. S. G., Matsubara, E., & Shoji, M. (2010). Amyloid β accelerates phosphorylation of tau and neurofibrillary tangle formation in an amyloid precursor protein and tau double-transgenic mouse model. Journal of Neuroscience Research, 88(16), 3547-3554. https://doi.org/10.1002/jnr.22516