GA therapy modulates α- and β-secretase activities in brains from APP/PS1 mice.
A and B, there are no between-groups differences on Adam10 or Bace1 mRNA expression in APP/PS1 brains after GA treatment. Data are expressed as relative-fold over WT-V mice. Data for A and B were obtained from APP/PS1 mice that received vehicle (APP/PS1-V, n = 12) or GA (APP/PS1-GA, n = 12) for 6 months commencing at 12 months of age. WT mice treated with vehicle (WT-V, n = 12) or with GA (WT-GA, n = 12) were also included as controls. C and D, α- and β-secretase activity assay results are shown. Relative fluorescence units are shown on the y axis, and reaction time is represented on the x axis. Cell-free β-secretase inhibitor activity assay results are shown (E). Results are expressed as % of β-secretase inhibitor activity on the y axis relative to 100% initial activity of β-secretase in the absence of GA. Data for A and B were obtained from APP/PS1 mice that received vehicle (APP/PS1-V, n = 12) or GA (APP/PS1-GA, n = 12) for 6 months commencing at 12 months of age. Data for C and D are presented as mean ± S.D. Statistical comparisons for A and B are between-groups. Statistical comparisons for E are between-doses. ***, p < 0.001 for APP/PS1-GA versus APP/PS1-V mice. *, p < 0.05 for 6.25 or 12.5 μm
versus 1.563 μm and similar results were observed in 2 to 3 independent experiments.