Fig. 3

TREM2 deficiency leads to altered microglial activation. a IHC staining was performed on 30 μm thick sagittal sections from 6-month hTau (Trem2 ^+/+) and hTau;Trem2 ^−/− mice (n = 6 per group; equal males and females) revealing altered morphological activation. b qRT-PCR was performed on hemi-brains from 6- and 12- month hTau (Trem2 ^+/+) and B6 control mice (n = 3–4 per group), revealing significantly upregulated TREM2 transcripts over time. c and d Individual microglia were selected randomly, isolated, thresholded, and skeletonized for analysis (20–30 per genotype) and compared between hTau and hTau;Trem2 ^−/− mice within cortex and CA3 region of the hippocampus. (e,l) IHC staining was performed on hTau (Trem2 ^+/+) and hTau;Trem2 ^−/− mice using antibodies against the pan-macrophage marker F4/80 (n = 6 per group). f, g Iba1 transcripts were analyzed from 6-month hTau (Trem2 ^+/+ ) and hTau;Trem2 ^−/− mice using qRT-PCR (n = 4–6 mice per group) alongside IHC staining with Iba1 (n = 6 per group) to perform a cell count which revealed no differences in the levels of Iba1 produced, or in the total number of cells/area h-k Detailed quantification of microglial morphology revealed decreased soma, cell area, branches, and branch points in TREM2 deficient mice compared to wild type hTau. At least two independent experiments were performed for each analysis. Error bars represent SEM., (b,f,l) Student’s t; (h-k) 2-way ANOVA with Sidak multiple comparisons correction) * P < 0.05. **, P < 0.01, ***, P < 0.001