Figure 6.

CF₃CN alleviates inflammation, inhibits AEP activation, and reduces the concentrations of AEP-derived APP fragments and Tau fragments. (A) Western blot showing the processing of APP and Tau by AEP. CF₃CN significantly inhibited AEP activation by phosphorylation of AEP T322, which attenuated Tau and APP cleavage. (B) Pro-inflammatory cytokine IL-6 was determined by ELISA kit. Chronic CF₃CN treatment significantly decreased the IL-6 production in mice brains compared with that of the age-related vehicle-treated mice (n = 5 in each group, data are shown as mean ± SEM **p < 0.01, one-way ANOVA). (C) AEP enzymatic activity analysis (n = 5 in each group, data are shown as mean ± SEM, *P < 0.05, **P < 0.01 compared with vehicle-treated mice brains, one-way ANOVA). (D) CF₃CN repressed AEP expression levels in 5xFAD mice. Immunofluorescence showing the presence of AEP positive cells in hippocampus of both vehicle- and CF₃CN-treated mice (scale bar, 50 μm). (E) CF₃CN inhibits AEP activation and reduces delta-secretase-derived APP fragments. Immunofluorescence staining of cortex from 5xFAD mice brains with AEP antibody (green), cleaved APP C586 fragment antibody (red), and DAPI (blue). (F) CF₃CN inhibits AEP activation and reduces delta-secretase-derived Tau fragments. Immunofluorescence staining of cortex from 5xFAD mice brain with cleaved Tau N368 fragment antibody (red), AT8 antibody (green), and DAPI (blue).