Inhibition of mTORC1 rescued long term and remote memory deficits in 5XFAD mice following PTZ kindling. (A) Experimental design in wild-type (WT) and 5XFAD mice, involving PTZ kindling starting from 3 months, rapamycin treatment starting from 3.5 months, cognitive assessment from 6.5–7 months and euthanasia for biochemical analyses at 7 months. (B) Associative long-term (test at 24 h post-training) and (C) remote memory (test at 14 days post-training) assessed with contextual fear conditioning test measuring % of time freezing relative to freezing pre-stimuli on training day. (D) Spatial working memory evaluated by % spontaneous alternation in the Y-maze. (E) Self-care assessed by nest building. Box and whisker plots display minimum, maximum and all quartiles. Scatter plots display all data-points, with mean ± SEM. Closed symbols represent males and open symbols represent females. n = 12–13 for each group. *P < 0.05, **P < 0.01, ***P < 0.001. ^!Treatment × Kindling interaction, P < 0.01; ^&Genotype × Sex interaction, P < 0.01; ^XGenotype × Kindling × Treatment interaction, P < 0.01; ^†Kindling effect, P < 0.05; ^#Genotype effect, P < 0.01.