Fig. 2 Increase of phosphorylated tau in the hippocampus of dox-administered hTau368 mice. a Diagram of human tau protein structure and phosphorylation epitopes measured in this study. b, c Dox treatment for 2 months showed no infuence on tau expression and phosphorylation in wild-type mice. Unpaired Student’s t-test, P > 0.05, n = 3 mice in each group. d, e Dox-treated hTau368 mice had higher levels of phosphorylated tau in the RIPA-soluble lysate of hippocampus. Homozygotes showed much more prominent pTau increase than hemizygotes. One-way ANOVA followed by Tukey’s multiple comparisons tests, *P < 0.05, **P < 0.01, ***P < 0.001, compared with the Veh group (n = 4 mice); ^#P < 0.05, Dox-Homo (n = 3 mice) compared with the Dox-Hemi group (n = 3 mice). f-h pTau aggregation in the hippocampus of Dox-treated hTau368 mice, detected by immunostaining for pS181, pS199 and AT8 tau. One-way ANOVA followed by Tukey’s multiple comparisons tests, ***P < 0.001, n = 3 mice in each group. i, j Dox-treated homozygous hTau368 mice had high levels of pTau in the RIPA-insoluble lysate of hippocampus. One-way ANOVA followed by Tukey’s multiple comparisons tests, *P < 0.05, compared with the Veh group, n = 3-4 mice in each group