%0 Journal Article %J J Alzheimers Dis %D 2018 %T In Vivo Visualization of Tau Accumulation, Microglial Activation, and Brain Atrophy in a Mouse Model of Tauopathy rTg4510. %A Ishikawa, Ai %A Tokunaga, Masaki %A Maeda, Jun %A Minamihisamatsu, Takeharu %A Shimojo, Masafumi %A Takuwa, Hiroyuki %A Ono, Maiko %A Ni, Ruiqing %A Hirano, Shigeki %A Kuwabara, Satoshi %A Ji, Bin %A Zhang, Ming-Rong %A Aoki, Ichio %A Suhara, Tetsuya %A Higuchi, Makoto %A Sahara, Naruhiko %K Animals %K Atrophy %K Benzothiazoles %K Brain %K Disease Models, Animal %K Female %K Magnetic Resonance Imaging %K Male %K Mice %K Mice, Transgenic %K Microglia %K Positron-Emission Tomography %K Receptors, GABA %K tau Proteins %K Tauopathies %X

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.

OBJECTIVE: 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.

%B J Alzheimers Dis %V 61 %P 1037-1052 %8 2018 %G eng %N 3 %1 http://www.ncbi.nlm.nih.gov/pubmed/29332041?dopt=Abstract %R 10.3233/JAD-170509