In Vivo Visualization of Tau Accumulation, Microglial Activation, and Brain Atrophy in a Mouse Model of Tauopathy rTg4510.

Autor:	Ishikawa A; National Institutes for Quantum and Radiological Science and Technology, Chiba, Japan.; Department of Neurology, Graduate School of Medicine, Chiba University, Chiba, Japan., Tokunaga M; National Institutes for Quantum and Radiological Science and Technology, Chiba, Japan., Maeda J; National Institutes for Quantum and Radiological Science and Technology, Chiba, Japan., Minamihisamatsu T; National Institutes for Quantum and Radiological Science and Technology, Chiba, Japan., Shimojo M; National Institutes for Quantum and Radiological Science and Technology, Chiba, Japan., Takuwa H; National Institutes for Quantum and Radiological Science and Technology, Chiba, Japan., Ono M; National Institutes for Quantum and Radiological Science and Technology, Chiba, Japan., Ni R; Institute of Biomedical Engineering/Institute for Pharmaceutical Sciences ETH Zurich, Switzerland., Hirano S; Department of Neurology, Graduate School of Medicine, Chiba University, Chiba, Japan., Kuwabara S; Department of Neurology, Graduate School of Medicine, Chiba University, Chiba, Japan., Ji B; National Institutes for Quantum and Radiological Science and Technology, Chiba, Japan., Zhang MR; National Institutes for Quantum and Radiological Science and Technology, Chiba, Japan., Aoki I; National Institutes for Quantum and Radiological Science and Technology, Chiba, Japan., Suhara T; National Institutes for Quantum and Radiological Science and Technology, Chiba, Japan., Higuchi M; National Institutes for Quantum and Radiological Science and Technology, Chiba, Japan., Sahara N; National Institutes for Quantum and Radiological Science and Technology, Chiba, Japan.
Jazyk:	angličtina
Zdroj:	Journal of Alzheimer's disease : JAD [J Alzheimers Dis] 2018; Vol. 61 (3), pp. 1037-1052.
DOI:	10.3233/JAD-170509
Abstrakt:	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.
Databáze:	MEDLINE
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