@article{oai:repo.qst.go.jp:00048782,
 author = {Ishikawa, Ai and Tokunaga, Masaki and Maeda, Jun and Minamihisamatsu, Takeharu and Shimojo, Masafumi and Takuwa, Hiroyuki and Ono, Maiko and Ni, Ruiqing and Hirano, Shigeki and Kuwabara, Satoshi and Ji, Bin and Zhang, Ming-Rong and Aoki, Ichio and Suhara, Tetsuya and Higuchi, Makoto and Sahara, Naruhiko and 石川 愛 and 徳永 正希 and 前田 純 and 南久松 丈晴 and 下條 雅文 and 田桑 弘之 and 小野 麻衣子 and 倪 遑伯 and 平野 成樹 and 季 斌 and 張 明栄 and 青木 伊知男 and 須原 哲也 and 樋口 真人 and 佐原 成彦},
 issue = {3},
 journal = {Journal of Alzheimer's Disease},
 month = {Jan},
 note = {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.},
 pages = {1037--1052},
 title = {In Vivo Visualization of Tau Accumulation, Microglial Activation, and Brain Atrophy in a Mouse Model of Tauopathy rTg4510},
 volume = {61},
 year = {2018}
}