FIGURE 4.

Transgene‐induced Tyrobp upregulation increases apparent stoichiometry of TAU phosphorylation and microglial activation in 4‐month‐old MAPT^P301S mice. A, Western blot analyses of phosphorylated TAU on S202 or T205 epitopes (AT8 and pT205 antibodies) and total human TAU (HT7 antibody) in cortical homogenates from wild‐type, MAPT^P301S (PS19), and MAPT^P301S;Iba1^Tyrobp mice at 4 months‐old. n = 4–9 mice per group. B, Densitometric analyses of western blots presented in (A) standardized to GAPDH or HT7. C, Representative images of DAB‐immunohistochemistry with antibody pT205 in 4‐month‐old MAPT^P301S and MAPT^P301S;Iba1^Tyrobp mice. Scale bar = 200 μm. D, Left panel: representative images of anti‐IBA1 immunohistochemistry on the same groups described in (C). Scale bar = 200 μm. Additional representative pictures are presented in Figure S2 in supporting information. Right panel: western blot‐AT8/GAPDH quantification plotted against anti‐IBA1 immunoreactivity in the cortex. Linear regression with trend line (red line) and 95% confidence intervals (black lines) are indicated. E, Representative images of double‐label immunofluorescence with anti‐IBA1 and anti‐CD68 antibodies in the piriform cortex on the same groups described in (C). Scale bar = 500 μm. F, Real‐time quantitative polymerase chain reaction analyses of microglial gene mRNAs in the hippocampus of MAPT^P301S and MAPT^P301S;Iba1^Tyrobp mice at 4 months of age. N = 7–11 per group. Error bars represent means ± standard error of the mean. Statistical analyses were performed using a one‐way analysis of variance followed by a Tukey's post hoc test for (B) or a Student t‐test for (B) when *t is indicated and (F), *P < .05, **P < .01, ***P < .001, ****P < .0001