(A to F) Six-month-old 5XFAD mice (n=6/group in two independent experiments) and 5XFAD-PparaΔAstro mice (n=7/group in two independent experiments) were orally administered with GFB-RA [the combination of gemfibrozil (8 mg/Kg/day) and retinoic acid (150 IU/day)] or vehicle (0.5% methylcellulose). Label color code: bottom right. After 60 days of treatment, behavioral tests [Barnes maze (A to C), T maze (D and E), and novel object recognition (F)] were performed to evaluate memory improvement in 5XFAD mice (n=6/group) and 5XFAD-PparaΔAstro mice (n=7/group). Data are mean ± SEM of 6 to 7 mice per group. *P<0.05, ***P<0.001, and NS denotes not significant by one-way ANOVA followed by Tukey’s multiple comparison test.