Fig. 3

3R and 4R tau accumulation and tau hyperphosphorylation in the monkey hippocampus after hTau overexpression. A Representative images of 3R tau immunostaining demonstrate the accumulation of 3R tau within the monkey hippocampus. Compared to the accumulation of endogenous 3R tau (top), the accumulation of 3R tau increased significantly after 6 weeks (middle) and 50 weeks (bottom) of hTau overexpression. Scale bar, 100 mm. B Representative images of 3R tau and NeuN costaining show the accumulation of 3R tau in neuronal somas and neurites in the monkey hippocampus. Scale bar, 10 mm. C Quantifications of the percentage of 3R tau-positive neurons within all the NeuN⁺ cells in the monkey hippocampus. ***P < 0.001; ****P < 0.0001. One-way ANOVA with Tukey’s post hoc test. N = 5. D Representative images of 4R tau immunostaining demonstrate the accumulation of 4R tau within the monkey hippocampus. Compared to the accumulation of endogenous 4R tau (top), the accumulation of 4R tau increased significantly after 6 weeks (middle) and 50 weeks (bottom) of hTau overexpression. Scale bar, 100 mm. E Representative images of 4R tau and NeuN costaining show the accumulation of 4R tau in neuronal somas and neurites in the monkey hippocampus. Scale bar, 10 mm. F Quantifications of the percentage of 4R tau-positive neurons within all the NeuN.⁺ cells in the monkey hippocampus. Note the dramatic increase in the percentage of 3R/4R tau-positive neurons after 6 and 50 weeks of hTau overexpression. **P < 0.01; ****P < 0.0001. One-way ANOVA with Tukey’s post hoc test. N = 5. G Representative images of phospho-tau (Ser202, Thr205) immunostaining demonstrate the dramatic increase in phospho-tau (Ser202, Thr205) in the monkey hippocampus after 6 weeks of AAV-induced tau overexpression. Insets show higher magnification of the CA1 regions. Scale bar, 1 mm (left) and 20 mm (right, inset). H Representative images of phospho-tau (Thr231) immunostaining show the robust increase in phospho-tau (Thr231) in the monkey hippocampus after 6 weeks of AAV-induced tau overexpression. These results suggest the accumulation of paired helical filaments (PHFs, the building blocks of NFTs). Insets show higher magnification of the CA4 regions. Scale bar, 500 mm (left) and 10 mm (right, inset)