Figure 2: Administration of donepezil in APP/PS1 double transgenic mice.

Donepezil (DNPZ) in drinking water was administered to 50-week-old APP/PS1 male mice (water, n = 9; 0.1 and 1 mg/kg/day of donepezil, n = 6 and 5) for 10 weeks and compared to age-matched wild type (WT, n = 13). Y-maze tests were performed at every week for 10 weeks. After the last set of Y-maze test, Aβ plaques in brains were stained by thoflavin-S. (A) Experiment schedule (LOQ: level of quantification). (B) (%) Alternations of Y-maze tests. Multiple sets of Y-maze tests were analysed by two-way repeated measures ANOVA between wild type and APP/PS1 mice with various donepezil dosages followed by Bonferroni’s post-hoc test (See in Supplementary Table 2 for statistical analyses). (C) Hippocampal region (bregma −1.58~−2.18 mm, 6 slides/mouse) of the mouse brain with thoflavin-S staining (scale bar, 400 μm). (D) Quantifications of number and (E) area of stained Aβ plaques. ImageJ software was used to quantify numbers and pixel areas of Aβ plaques. Numbers of mice for biochemical analyses are described in Methods. One-way ANOVA with Bonferroni’s post-hoc comparisons were performed in statistical analyses. All the error bars represent the SEMs. (*P < 0.05, **P < 0.01, ***P < 0.001).