Fig. 6.
Disruption of PPARα exacerbates cerebral Aβ load and decreases lifespan in 5XFAD mice. (A) Representative images of coronal sections from 5- to 6-mo-old 5XFAD (A1), 5- to 6-mo-old 5X/Pparα−/− (A2), 10- to 12-mo-old 5XFAD (A3), and 10- to 12-mo-old 5X/Pparα−/− (A4) mice colabeled with thioflavin-S (Thio-S, green) and 6E10 (red). (B) Quantification of Thio-S-positive area as a percentage of total area in the cortex (CTX) and hippocampus (HPC) of 5XFAD and 5X/Ppara−/− mice. All values represent the mean ± SEM and represent n = 14, 13, 19, and 18 for 5- to 6-mo-old 5XFAD, 5- to 6-mo-old 5X/Ppara−/−, 10- to 12-mo-old 5XFAD, and 10- to 12-mo-old 5X/Ppara−/− mice, respectively. (C and D) Representative immunoblots (C) and quantification of 6E10-detected Aβ (D) expression in TBS fractions from 2- and 6-mo-old WT, 5XFAD (5X), and 5X/Pparα−/− (5X/α−/−) hippocampi. Values are corrected for α-tubulin and indicate the mean ± SEM relative to WT. (E) ELISA quantification of human Aβ1–42 in serially extracted TBS (Top) and TBS+1% Triton X-100 (TBS-Tx; Bottom) fractions from 5XFAD and 5X/α−/− hippocampi. (F) Kaplan–Meier survival analysis of WT (n = 15), Pparα−/− (n = 13), 5XFAD (n = 19), and 5X/α−/− (n = 16) animals across 24 mo. Plus (+) symbols represent censored cases. All values represent the mean ± SEM and represent n = 4 (C and D) or 5 (E) for each genotype and age. *P < 0.05, **P < 0.01, and ***P < 0.001, using Student’s t test, and #P < 0.01, using Breslow Generalized Wilcoxon χ2. (Scale bar, 500 µm.) IB, immunoblot; OD, optical density. ●, nonspecific band.