Title | In Vivo Visualization of Tau Accumulation, Microglial Activation, and Brain Atrophy in a Mouse Model of Tauopathy rTg4510. |
Publication Type | Journal Article |
Year of Publication | 2018 |
Authors | Ishikawa, A, Tokunaga, M, Maeda, J, Minamihisamatsu, T, Shimojo, M, Takuwa, H, Ono, M, Ni, R, Hirano, S, Kuwabara, S, Ji, B, Zhang, M-R, Aoki, I, Suhara, T, Higuchi, M, Sahara, N |
Journal | J Alzheimers Dis |
Volume | 61 |
Issue | 3 |
Pagination | 1037-1052 |
Date Published | 2018 |
ISSN | 1875-8908 |
Keywords | Animals, Atrophy, Benzothiazoles, Brain, Disease Models, Animal, Female, Magnetic Resonance Imaging, Male, Mice, Mice, Transgenic, Microglia, Positron-Emission Tomography, Receptors, GABA, tau Proteins, Tauopathies |
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. 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. |
DOI | 10.3233/JAD-170509 |
Alternate Journal | J. Alzheimers Dis. |
PubMed ID | 29332041 |