Figure 2. Human APP expression decreases Ppara expression and PPARα downstream target genes in old mice.

Brain frontal cortex tissues from transgenic mice overexpressing nonmutated human APP (hAPP_WT) and WT littermates were analyzed at 3–4, 6–8, and 11–12 months old (mo). (A) The expression of hAPP was investigated in mice brain lysates (n = 6 of each) by immunoblot analysis (see complete unedited blots in the supplemental material) with the specific WO2 antibody recognizing hAPP and anti-APP C-terminal antibody recognizing both hAPP and endogenous APP (APP). Blots were further probed using anti–α-tubulin antibody. (B) Relative density of APP expression was compared with α-tubulin. Results were normalized compared with 3–4 mo WT and are shown as mean ± SEM. A Kruskal-Wallis test followed by Dunn’s multiple comparisons posttest was used to assess significance of the mean (APP expression at 3–4, 6–8, and 11–12 mo, P < 0.05). (C–F) Quantitative real-time PCR analyses (n = 7 of each) for Ppara, Acox1, Cpt1a, and Pdk4 mRNA levels. Results were normalized to Rpl32 mRNA, compared with 3–4 mo WT, and shown as mean ± SEM. A Kruskal-Wallis test followed by Dunn’s multiple comparisons posttest was used to assess significance of the mean (11–12 mo hAPP_WT mice: Ppara mRNA, P = 0.012, Acox1 mRNA, P = 0.0008, Cpt1a mRNA, P = 0.031; Pdk4 mRNA, P = 0.022), *P < 0.05, ***P < 0.001.