Fig. 1.
ASOs reduce TREM2 throughout the brain of APP/PS1 mice. (A) Brain tissue from 11-mo-old APP/PS1 and nontransgenic (NonTg, n = 5) mice was analyzed for Trem2 mRNA by qRT-PCR 1 mo following intracerebroventricular injection of inactive ASO or Trem2 KD ASO (n = 3/group). Tissues from untreated APP/PS1 mice at 10 mo of age (n = 3) were included as a control. mRNA was normalized to GAPDH and expressed as mean ± SEM; one-way ANOVA with Tukey’s multiple comparison test; *P < 0.05, **P < 0.01, ***P < 0.001 versus NonTg; ###P < 0.001 versus APP/PS1 10 mo and inactive ASO; ns, nonsignificant. Individual mice are depicted as open squares. (B) Representative images of Trem2 immunohistochemistry from brain tissue contralateral to the ASO injection from NonTg and ASO-treated APP/PS1 mice. The CA3 regions of the hippocampus are shown, with arrowheads indicating TREM2-positive areas. (Scale bar, 250 μm.) (C) Representative images of Iba1 (green) and TREM2 (red) immunofluorescence within the retrosplenial cortex are shown, with arrowheads indicating colocalized (yellow) regions. (Scale bar, 50 μm.)