Figure 7
XYT472B attenuates behavior deficits and Aβ pathology of APP/PS1 mice. (a) Swimming velocities of mice in all groups during the probe trials on day 4 and day 7. (b) XYT472B treatment ameliorates the cognitive deficits of APP/PS1 mice in Morris water maze. APP/PS1 mice show a slower learning curve compared with WT littermates with statistical significance on days 3, 4, 6 and 7. This impairment was partially improved by XYT472B treatment (with statistical significance on days 6 and 7). n=16 for each group. #P<0.05, ##P<0.01, *P<0.05, determined by two-way ANOVA. (c) Representative brain immunofluorescent images of vehicle- or XYT472B-treated mice. (d) Statistical analyses show that 6E10-positive Aβ plaques and GFAP-positive area were reduced by XYT472B treatment. Scale bar, 500 μm. (e) Reduced Aβ levels in hippocampus and prefrontal cortex of XYT472B-treated mice. Extracts from hippocampus or cortex were prepared and subjected to sandwich ELISAs for human Aβ40 and Aβ42. (f) BACE1, γ-secretase and α-secretase activities were unaltered by chronic treatment of XYT472B. Fluorogenic substrate assays were performed with the membrane fractions extracted from mouse hippocampi or cortices. (d–f) *P<0.05, **P<0.01, determined by unpaired Student’s t-test. (g) Chronic XYT472B treatment shows no effects on secretase expression or substrate processing. Extracts from hippocampus were analyzed by western blotting. (h) Chronic XYT472B treatment attenuates the interaction between BACE1 and PS1ΔE9 in vivo. Vehicle- or XYT472B-treated APP/PS1 mouse brains were homogenized, and purified membrane fractions were incubated with IgG or MAB-1563 antibody for immunoprecipitation. Cx, cortex; Hp, hippocampus.
