Fig. 5.

Extended treatment with AMPA decreases Aβ levels through clearance. a 2–4 month old APP/PS1 mice were treated with either 5 μM AMPA (n = 6) or aCSF (n = 8) via reverse microdialysis for 14 h. Tissue surrounding the microdialysis probe was analyzed via Western blot for full-length APP, CTF-β, sAPPα, sAPPβ, and total sAPP, and no significant change was observed between treatment groups (two-way ANOVA, Sidak post hoc test). Bands were normalized to GAPDH and displayed relative to control. Blot images are representative examples. b APP/PS1 mice were treated with 14 h of AMPA (n = 6) or vehicle (n = 7). With microdialysis collection ongoing, animals were administered a 4 mg/kg subcutaneous injection (s.c.) of LY411575, a γ-secretase inhibitor, or vehicle (corn oil). c ISF Aβ half-life for each treatment group was calculated by taking the slope of the semi-log plot of concentration versus time for the time points between drug delivery and the plateauing of Aβ concentrations. Mice treated with 5 μM AMPA had an Aβ half-life of 0.9 ± 0.1 h compared to a half-life of 1.5 ± 0.2 h for the mice treated with aCSF (p = 0.0298, two-tailed t-test)