Figure 6. CTFα and CTFβ accumulate upon treatment with a γ-secretase inhibitor.

YAC-AβPP transgenic mice (12–15 weeks of age) were administered saline (C) or the γ-secretase inhibitor LY411575 for 8 or 12 hours. Retina (RET, A–B), retinal pigment epithelium (RPE, C–D) and total brain (E–F) extracts from control and treated mice were analyzed by Western blotting with the O443 antibody. The bar graphs show a plot of the relative density (n=2) of CTFα and CTFβ bands after normalization to the full-length AβPP bands. With an n of 2, we are still able to see significant increases in CTFα and CTFβ after LY411575 treatment by ANOVA (Fisher’s Protected Least Significant Difference (PLSD)) in the retina (P<0.0001) and RPE (CTFβ P<0.01; CTFα P<0.0001). Brain CTFβ was significantly increased (P<0.01) for 8 and 12 h but CTFα was significant only at 12 h). CTFβ/CTFα ratio was highest in the brain (39±7%) but significantly lower in the retina (15±6%; P<1E-4) and RPE (19±6%, P<0.001).