A, B Immunofluorescent staining of Aβ (red) in the frontal cortex region of brains, and T22 (red) in the hippocampus CA1 region of brains from 6-month-old vehicle, 12-HHTrE, or PGE2-treated C/EBPβ Tg mice. Mice received IP injection of the diluted 12-HHTrE, or PGE2 solution at the dose of 5 mg/kg twice a week for 4 weeks. Scale bar: 40 μm. C, D Quantitative analysis of positive plaques and PHFs (left panel, n = 8 biologically independent samples in each group, data are shown as mean ± SEM, one-way ANOVA and Bonferroni’s multiple comparison test). E Mouse Aβ40 and Aβ42 ELISA. (n = 5 biologically independent samples in each group, data are shown as mean ± SEM, one-way ANOVA and Bonferroni’s multiple comparison test). F Sarkosyl-insoluble fractions were blotted with antibodies against Aβ (4G8), or Tau T22 for Tau oligomers (representative of 3 mice). G Silver staining in cortex and hippocampus. Scale bar: 50 μm. H Quantitative analysis of (G). (n = 8 biologically independent samples in each group, data are shown as mean ± SEM, one-way ANOVA and Bonferroni’s multiple comparison test). I The dendritic spines from the apical dendritic layer of the hippocampus CA1 region were analyzed by Golgi staining. (upper panel, Scale bar: 10 μm). Quantitative analysis of Golgi staining (n = 8 biologically independent samples in each group, data are shown as mean ± SEM, one-way ANOVA and Bonferroni’s multiple comparison test) (lower panel). J Electron microscopy analysis of synapses, the number of synapses in CA1 region of 12-HHTrE, or PGE2-treated C/EBPβ Tg mice were decreased compared with vehicle-treated mice. Arrows indicate the synapses. Scale bar, 1 μm. K Quantitative analysis of synapses in CA1, (n = 5 biologically independent samples per group, mean ± SEM, one-way ANOVA and Bonferroni’s multiple comparison test). L, M Morris Water Maze analysis of cognitive functions. 12-HHTrE, or PGE2-treated C/EBPβ Tg mice exacerbated the learning and memory dysfunctions, but does not affect motor function. (mean ± SEM.; n = 7 biologically independent samples per group, one-way ANOVA and Bonferroni’s multiple comparison test).