Figure 3. Characterization of brain tau pathology by immunohistochemistry and Gallyas-Braak silver staining. A, AT8 (top) and AT100 (bottom) immunoreactivity in MaptP290S KI and AppNL-G-FxMaptP290S KI mice at 24 months of age. AT8- or AT100-immunoreactive cells were quantified at 3, 6, 12, 18, and 22–24 months in 50 μm whole-brain coronal sections. Results shown are the mean ± SEM. Significance between genotypes and adjacent time-points within a genotype is reported for two-way ANOVA with Tukey’s post hoc analysis (*p < 0.05, **p < 0.01, ****p < 0.0001). Quantitation values of AT8 staining in MaptP290S KI mice were as follows: 3 months, n = 6 (3 M, 3 F); 6 months, n = 6 (3 M, 3 F); 12 months, n = 8 (4 M, 4 F), 18 months, n = 8 (4 M, 4 F); and 22–24 months, n = 6 (3 M, 3 F). Values in AppNL-G-FxMaptP290S KI mice were as follows: 3 months, n = 6 (3 M, 3 F); 6 months, n = 8 (4 M, 4 F); 12 months, n = 8 (4 M, 4 F); 18 months, n = 8 (4 M, 4 F); 22–24 months, n = 4 (2 M, 2F). Brain sections from 4 (2 M, 2 F) 18-month-old AppNL-G-FxMaptP290S KI mice were not available at the time of AT100 staining. B, Representative images of Gallyas-Braak silver staining at 24 months of age in MaptP290S and AppNL-G-FxMaptP290S KI mice. C, Timeline depicting the appearance of cells labeled with Gallyas-Braak silver stain in MaptP290S KI and AppNL-G-FxMaptP290S KI mice. Values were as follows: at 3 and 6 months, n = 3 (2 M, 1 F); at 12 and 18 months, n = 8 (4 M, 4 F); at 22–24 months, n = 4 (2 M, 2 F). D, In situ electron microscopy of Gallyas-Braak silver-stained brain sections from 24-month-old AppNL-G-FxMaptP290S KI mouse showing labeled filamentous content of a tau inclusion (i) within the cell body of a neuron, adjacent to a nucleus (n).