Fig. 4

Trem2 H157Y reduces glial responses in 5xFAD mice at 8.5 months of age. A. Representative images of IBA1 immunostaining are shown for each genotype. Scale, 400 µm. B-C. Cortical (B) and hippocampal (C) IBA1⁺ area percentages were quantified and normalized to WT. D. The correlation between IBA1⁺ area percentages and Aβ42 in GND lysates is shown with correlation coefficient (r) and significance symbols. E–F. Cortical (E) and hippocampal (F) CD68⁺ area percentages were quantified for each genotype. G. Correlation between CD68⁺ area percentages and Aβ42 in GND lysates are shown with correlation coefficient (r) and significance symbols. H. Representative images of CD68 immunostaining are shown for each genotype. Scale, 400 µm. I-J. Cortical (I) and hippocampal (J) TREM2⁺ area coverages were quantified and normalized to WT mice. K, Representative confocal images of X34, TREM2, IBA1 and MOAB2 co-staining are shown for each genotype. Scale, 10 µm. L. The correlation between TREM2⁺ and IBA1⁺ area percentages is shown with correlation coefficient (r) and significance symbols. M. Representative confocal images of IBA1 and X34 co-staining are shown for each genotype. Scale, 10 µm. N. Microglial numbers surrounding X34 signal were counted and quantified within a radius of 30 µm for each genotype. O. Plaque (X34) area coverages by microglia (MG) (IBA1) were quantified, ratioed to microglia number and normalized to WT within a radius of 30 µm for each genotype. N–O. N = 4 mice per genotype at 8.5 months of age. Data are presented as Mean ± SEM. Unpaired t-tests were used. P-Q. Cortical (P) and hippocampal (Q) GFAP⁺ area percentages were quantified and normalized to WT mice. R. Representative images of GFAP immunostaining are shown for each genotype at 8.5 months of age. Scale, 400 µm. A-L, P-R. N = 19–24 mice per genotype at 8.5 months of age, mixed sex. Data are presented as Mean ± SEM. Kruskal–Wallis tests with uncorrected Dun’s multiple comparisons were used in B, C, E, F, I, J, P and Q. N.S., not significant. *p < 0.05. **p < 0.01. ***p < 0.001. ****p < 0.0001