(a) Time course of behavioural tests. EPPS, 0 (TG(−), male, n=15), 10 (TG(+), male, n=11) or 30 mg kg−1 per day (TG(++), male, n=8), was orally given to 10.5-month-old APP/PS1 mice for 3.5 months and their behavioural changes were compared with age-matched WT mice (WT(−), male, n=16). (b) Pre-EPPS treatment evaluation of cognitive deficits; 10.5-month-old WT mice (male, n=18) and age-matched APP/PS1 TG mice (male, n=13) were used in Y-maze tests, to obtain the % alternation before the administration of EPPS. The data indicated cognitive deficits in 10.5-month-old APP/PS1 mice (P<0.0001). (c–i) Y-maze, fear-conditioning and Morris water maze tests on 14-month-old APP/PS1 mice after EPPS administration for 3.5 months total. (c) Per cent alternation on Y-maze. From the top, P=0.000, 0.020, 0.008, 0.010. (d) Total entry number into each arm of the Y-maze test. (e) Per cent total freezing from contextual fear conditioning. From the top, P=0.000, 0.036, 0.038. (f) Per cent total freezing in the cued task, P=0.025. (g) Hidden platform test (significances, see Supplementary Table 3) and (h) the probe test in the Morris water maze, P=0.003, 0.033. (i) Swim speeds of the probe test (crossing number of located hidden platform analysis, see Supplementary Fig. 2I). (j) Dose-dependent evaluation of EPPS-induced memory alterations. EPPS was orally given to 12-month-old APP/PS1 TG male mice in 0, 0.1, 1 or 10 mg kg−1 per day (n=7–9) dosages for 3 months. Per cent alternation on Y-maze (P=0.005, 0.041). The error bars represent the s.e.m. One-way analysis of variance followed by Bonferroni’s post-hoc comparisons tests were performed in all statistical analyses (*P<0.05, **P<0.01, ***P<0.001; other comparisons were not significant).