Fig. 7
BACEi-induced alterations in APP metabolism. a–l Beginning at 1 month of age, J20 mice (+) and WT (−) controls were treated for 2 or 3 months (a, b) or 6–8 months (c–l) with the BACEi NB-360 (+) or placebo (−). Levels of APP and its metabolites were measured in the indicated brain regions at the end of treatment. a, b Hippocampal levels of Aβ1-x (a) and Aβ1–42 (b) were determined by ELISA. c, d Levels of Aβ oligomers in the hippocampus (c) and cortex (d) were determined by 3D6/3D6 MSD ELISA as in Fig. 2c. Average signals in placebo-treated WT mice were used for background subtraction. e, f Western blots depicting hippocampal signals for full-length (FL)-APP (e) and CTFs (f). Actin was used as a loading control. g–l Quantitations of western blot signals for the indicated brain regions corresponding to FL-APP (g, j), C99 (h, k) and C83 (i, l). Mean levels in placebo-treated WT mice were defined as 1.0. n = 4–6 (a, b), 7–14 (c, d), and 8–16 (g–l) mice per group. All groups in (a, b) included males and females, while groups in (c–l) consisted of females only, as male mice were used for the behavioral analyses in Fig. 8. *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001 vs. placebo-treated WT or as indicated by brackets, based on multiple Welch t-tests with Holm-Sidak correction. Values are means ± SEM