TY - JOUR T1 - Comparative In Vitro and In Vivo Quantifications of Pathologic Tau Deposits and Their Association with Neurodegeneration in Tauopathy Mouse Models JF - Journal of Nuclear Medicine JO - J Nucl Med SP - 960 LP - 966 DO - 10.2967/jnumed.117.201632 VL - 59 IS - 6 AU - Ruiqing Ni AU - Bin Ji AU - Maiko Ono AU - Naruhiko Sahara AU - Ming-Rong Zhang AU - Ichio Aoki AU - Agneta Nordberg AU - Tetsuya Suhara AU - Makoto Higuchi Y1 - 2018/06/01 UR - http://jnm.snmjournals.org/content/59/6/960.abstract N2 - Fibrillary tau aggregates in Alzheimer disease and allied neurodegenerative disorders have been visualized in vivo by PET, whereas mechanistic links between PET-detectable tau deposits and neurotoxicity remain elusive. Here, we took advantage of transgenic mouse models of tauopathies to evaluate associations between PET and postmortem measures of tau probe binding and their relation to neuronal loss. Methods: PET with a tau probe, 11C-PBB3 (2-((1E,3E)-4-(6-(11C-methylamino)pyridine-3-yl)buta-1,3-dienyl)benzo[d]thiazol-6-ol), and volumetric MRI were performed for transgenic rTg4510 mice and nontransgenic mice. Binding of 11C-PBB3 and its blockade by another tau binding compound, AV-1451 (-(6-fluoropyridine-3-yl)-5H-pyrido[4,3-b]indole), in homogenized brains of tauopathy patients and rTg4510 and PS19 mice were quantified, and 11C-PBB3–positive and phosphorylated tau lesions in sectioned brains of these mice were assessed. Results: In vivo 11C-PBB3 binding to the rTg4510 neocortex/hippocampus was increased relative to controls and correlated with local atrophy. In vitro 11C-PBB3 binding in the neocortex/hippocampus also correlated well with in vivo radioligand binding and regional atrophy in the same individual rTg4510 mice. By contrast, in vitro 11C-PBB3 binding was elevated in the brain stem but not hippocampus of PS19 mice, despite a pronounced loss of neurons in the hippocampus rather than brain stem. Finally, 11C-PBB3 and AV-1451 showed similar binding properties between mouse models and tauopathy patients. Conclusion: The present findings support the distinct utilities of 11C-PBB3 PET and MRI in rTg4510 and PS19 mice for quantitatively pursuing mechanisms connecting PET-detectable and PET-undetectable tau aggregations to neuronal death, which recapitulate 2 different modes of tau-provoked neurotoxicity. ER -