Tg2576 mice were assessed for activated microglia associated with Aβ plaques. (A) Representative images show that regardless of stress condition, all mice display Nab228-IR (+) Aβ plaques (blue) that are Thioflavin-S (+) (green) in the frontal cortex. However, RI mice showed significantly less Iba1-IR (+) activated microglia (red) around Aβ plaques without a decrease in overall Iba1-IR. (B) This effect is quantified by non-fluorescent immunoreactivity load ratios ± SEM of adjacent sections (F(2,21)=6.51, p=0.007) and (F(2,21)=6.51, p=0.007) (n=8/group). Fourteen mo old Tg2576 mice (n=10/group) were also tested on the Barnes maze (C) and fear conditioning (D). RI but not VS mice demonstrated significantly worse % success (F(3,35)=12.8, p<0.0001) compared to NS mice. In both context (F(2,20)=6.22, p=0.009) and cued (F(2,21)=5.98, p=0.01) fear conditioning, both VS and RI stressed Tg2576 mice froze significantly less than NS mice. Data show mean ± SEM. p*<0.05, **<0.01, ***<0.001 from NS. Scale bar = 100 μm.