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タイトル
  • In Vivo Visualization of Tau Accumulation, Microglial Activation, and Brain Atrophy in a Mouse Model of Tauopathy rTg4510
作成者
    • Ishikawa, Ai
    • Tokunaga, Masaki
    • Maeda, Jun
    • Minamihisamatsu, Takeharu
    • Shimojo, Masafumi
    • Takuwa, Hiroyuki
    • Ono, Maiko
    • Ni, Ruiqing
    • Hirano, Shigeki
    • Kuwabara, Satoshi
    • Ji, Bin
    • Zhang, Ming-Rong
    • Aoki, Ichio
    • Suhara, Tetsuya
    • Higuchi, Makoto
    • Sahara, Naruhiko
    • en 石川 愛
    • en 徳永 正希
    • en 前田 純
    • en 南久松 丈晴
    • en 下條 雅文
    • en 田桑 弘之
    • en 小野 麻衣子
    • en 倪 遑伯
    • en 平野 成樹
    • en 季 斌
    • en 張 明栄
    • en 青木 伊知男
    • en 須原 哲也
    • en 樋口 真人
    • en 佐原 成彦
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内容注記
  • Abstract Background: Tau imaging using PET is a promising tool for the diagnosis and evaluation of tau-related neurodegenerative disorders, but the relationship among PET-detectable tau, neuroinflammation and neurodegeneration is not yet fully understood. We aimed to elucidate sequential changes in tau accumulation, neuroinflammation and brain atrophy by PET and MRI in a tauopathy mouse model. Methods: rTg4510 transgenic (tg) mice expressing P301L mutated tau and non-tg mice were examined with brain MRI and PET imaging (analyzed numbers: tg = 17, non-tg = 13; age 2.5~14 months). As PET probes, [11C]PBB3 (Pyridinyl-Butadienyl-Benzothiazole 3) and [11C]AC-5216 were used to visualize tau pathology and 18-kDa translocator protein (TSPO) neuroinflammation. Tau pathology and microglia activation were subsequently analyzed by histochemistry. Results: PET studies revealed age-dependent increases in [11C]PBB3 and [11C]AC-5216 signals, which were correlated with age-dependent volume reduction in the forebrain on MRI. However, the increase in [11C]PBB3 signals reached a plateau at age 7 months, and therefore its significant correlation with [11C]AC-5216 disappeared after age 7 months. In contrast, [11C]AC-5216 showed a strong correlation with both age and volume reduction until age 14 months. Histochemical analyses confirmed the relevance of pathological tau accumulation and elevated TSPO immunoreactivity in putative microglia. Conclusion: Our results showed that tau accumulation is associated with neuroinflammation and brain atrophy in a tauopathy mouse model. The time-course of the [11C]PBB3- and TSPO-PET finding suggests that tau deposition triggers progressive neuroinflammation, and the sequential changes can be evaluated in vivo in mouse brains.
日付
    Issued2018-01
言語
  • eng
資源タイプ journal article
資源識別子 URI https://repo.qst.go.jp/records/48782
関連
  • PMID 29332041
  • DOI https://doi.org/10.3233/JAD-170509
収録誌情報
    • ISSN 1387-2877
      • Journal of Alzheimer's Disease
      • 巻61 号3 開始ページ1037 終了ページ1052
コンテンツ更新日時 2023-07-10