Figure 8. Inhibition of eicosanoid production reduces APP expression in aged 5XFAD transgenic mice.

5XFAD mice (5.5–6.0 months of age) were provided drinking water containing SC-560 and rofecoxib for a total of 7 days (COX group; 3 females and 6 males). Another group of similarly aged 5XFAD mice received the COX inhibitor mixture supplemented with licofelone (COX/Licof group; 5 females and 4 males). A group of age-matched 5XFAD mice received drinking water containing the vehicle only (5 females and 5 males). Quantification of total APP (22C11 antibody) normalized to GAPDH for cortical (A) and hippocampal (B) homogenates revealed a significant reduction in both the COX and COX/Licof treatment groups compared to the vehicle group. Primary immunoblots are shown for the COX/Licof-treated (CL) and vehicle-treated (V) mice, with lane loading randomized for study blinding during quantification. The 9 COX/Licof inhibitor-treated samples were run on each gel, with the 10 vehicle-treated samples split between the two gels. The relative APP/GAPDH value for each drug-treated mouse sample was normalized to the vehicle mean on each gel, with the final APP/GAPDH value consisting of the average sample value derived from the two separate gels. A similar analysis was conducted for the COX inhibitor treatment group. Statistical analyses consisted of a one-way ANOVA with a Tukey’s multiple comparison test. *p < 0.05; **p < 0.01, ***p<0.001.