Fig. 6

AMPA-mediated decrease in Aβ not due to changes in clearance-related proteins or proteases. 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 to determine levels of proteins involved in Aβ elimination and clearance. Bands were normalized to GAPDH and displayed relative to control. Blot images are representative examples. cFos protein expression was increased 2.9 ± 0.4 fold (p < 0.0001, two-way ANOVA, Sidak post hoc test) in the AMPA group compared to the controls. No other proteins showed a significant difference between treatment groups. b Reverse microdialysis was used to treat APP/PS1 mice (n = 7) with 10 μM thiorphan (neprilysin inhibitor), 25 μM GM6001 (broad-spectrum MMP inhibitor), or vehicle for 6 h, followed by 14 h of co-treatment with 5 μM AMPA. The Aβ concentrations in the last 3 h of each treatment were averaged and the differences between the end of inhibitor/vehicle treatment and after the addition of AMPA were compared. Inhibiting protease activity with thiorphan or GM6001 did not alter the decrease in ISF Aβ levels observed following AMPA treatment (p = 0.40, one-way ANOVA, Dunnet’s post hoc test). Data plotted as mean ± SEM