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. 2023 Oct 17;20(2):1013–1025. doi: 10.1002/alz.13493

FIGURE 4.

FIGURE 4

Genetic depletion of Ifnar1 reduces tau pathology in vivo. (A) Cortical cytokine profile of wildtype (n = 6 M), Ifnar1 +/+ P301S‐tau (n = 3 M, n = 4 F), Ifnar1 −/− P301S‐tau (n = 4 M, n = 3 F) mice at 22 weeks of age, measured by Luminex 48‐plex assay. Data presented are log2 of cytokine concentration (pg/mL), which was normalized to average of WT controls for each cytokine. Gray = not detected. (B) Replot of selected cytokines CXCL10 and CCL7 observed to be significantly different between Ifnar1 +/+ and Ifnar1 −/− P301S‐tau animals. Subanalysis of male‐only mice showed the same effects. (C) Representative images and (D) quantification of Iba1 staining in cerebral cortex of Ifnar1 +/+ P301S‐tau and Ifnar1 −/− P301S‐tau mice. Points represent n = 3/4 sections/mouse from Ifnar1 +/+ P301S‐tau (n = 3 M, n = 3 F), Ifnar1 −/− P301S‐tau (n = 3 M, n = 3 F) mice. (E) Representative images and (F) quantification of GFAP staining in hippocampus of Ifnar1 +/+ P301S‐tau and Ifnar1 −/− P301S‐tau mice. Points represent n = 3 or 4 sections/mouse from Ifnar1 +/+ P301S‐tau (n = 2 M, n = 2 F), Ifnar1 −/− P301S‐tau (n = 2 M, n = 2 F) mice. (G) Representative images and (H) quantification of AT8 staining in 22‐week‐old Ifnar1 +/+ P301S‐tau and Ifnar1 −/− P301S‐tau brain sections. Points represent average of n = 3 sections/mouse (at least n = 6 mice per group, n = 3 M and n = 3 F in each group). (I) Quantification of seeded tau aggregation in HEK293 cells expressing P301S tau‐venus, treated with spinal cord homogenate from Ifnar1 +/+ P301S‐tau, Ifnar1 −/− P301S‐tau at 14 weeks (n = 6 mice per group, n = 3 M and n = 3 F in each group) and 22 weeks (n = 7 mice per group). Points represent n = 3 technical replicates per animal. Scale bar = 100 μm for C, E and 1000 μm for G. Significance calculated by one‐way ANOVA for B, Welch's t‐test for D, F, and I, and Mann–Whitney test for H. *p < 0.05; **p < 0.01; ***p < 0.001; ****p < 0.0001; ns, not significant. Mean and SD are presented.