Fig. 5
Age/disease-dependent impairment of plaque-microglia interaction driven by Trem2R47H. a, b Quantification of cortical microglial morphology of wild-type (WT), Trem2R47H, 5xFAD, and 5xFAD/Trem2R47H revealed (a) increased dendrite length per IBA1+ cell in Trem2R47H compared to WT but (b) decreased average dendrite diameter. c, d Subiculum—representative confocal images from wild-type, Trem2R47H, 5xFAD, and 5xFAD/Trem2R47H mice at (c) 4- and (d) 12-months old stained with Thio-S for dense-core plaques (green), immunolabeled with 6E10 for diffused plaque (blue), and IBA1 for microglia (red). e–h Quantification of IBA1+ cell density and average volume in the (e, f) visual cortex and (g, h) subiculum at 4-months of age. In the cortex (e) a sex-dependent increase in microglia number and (f) a decrease in average microglial volume in the presence of Trem2R47H are found. g, h In the subiculum, a decrease in both microglial density (g) and volume (h) is observed in 5xFAD/Trem2R47H compared to 5xFAD. i -l IBA1+ cell density and average volume in the (i, j) visual cortex and (k, l) subiculum at 12-months-old. m–n Representative images of Thio-S (green) and IBA1 (red) colocalization in the subiculum at (m) 4-months and (n) 12-months old. o, p Quantification of percent colocalized volume of Thio-S+ and IBA1+ cell normalized to total Thio-S volume per field of view in the subiculum revealed decreased plaque-microglia interaction in 5xFAD/Trem2R47H at (o) 4-months with sex-differences but not at (p) 12-months old. n = 10–12. Data are represented as mean ± SEM. Two-way ANOVA followed by Tukey’s post hoc tests to examine biologically relevant interactions. Statistical significance is denoted by *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001