Fig. 3

Prenatal to early postnatal treatment with P021 prevents Tau pathology at 22 months of age in 3xTg-AD mice. a, b Western blot analysis of tau pathology in 4- and 22-month-old mice. c, d Densitometric quantification of blots after normalization with GAPDH or rabbit polyclonal antibody to total tau, R134D. P021 treatment reduced total tau (R134d) and human tau (43D); there was no increase in hyperphosphorylation of tau in 4-month-old 3xTg-AD mice as compared to the WT control but P021 treatment reduced the level of phosphorylation at AT8 site in the former (a, c). The level of hyperphosphorylation of tau at PHF1 and AT8 sites was increased in the hippocampus and the P021 treatment prevented it at 22 months in 3xTg-AD mice (b, d). e Immunostaining with PHF1 showed a decrease in CA1 area of the hippocampus in P021-treated 3xTg mice at age 22 months (a, b: the high magnification). f Analysis of percent area of PHF1 staining. Data were analyzed by two-way ANOVA followed by Tukey’s multiple comparisons test. Further intergroup comparisons were performed using unpaired, two-tailed t tests. At each age, n = 3–4 for WT-Vh, n = 4 for WT-P021, n = 4 for 3xTg-Vh, and n = 4 for 3xTg-P021. *P < 0.05, **P < 0.01, ***P < 0.001