Figure 4.
GA therapy promotes nonamyloidogenic and inhibits amyloidogenic APP processing. A, Western blots are shown using N-terminal APP pAb (N-APP), C-terminal sAPP-α mAb (2B3), or C-terminal anti-sAPP-β-sw mAb (6A1). We also used N-terminal amyloid-β1-17 mAb (82E1), which detects amyloidogenic APP cleavage fragments, including Aβ monomers and oligomers as well as phospho-C99 (P-C99) and nonphospho-C99 (C99). Actin is included as an internal reference control. Densitometry results are shown for ratios of sAPP-α or sAPP-β to APP (B and C) and for P-C99 or C99 to actin (D). E, abundance of Aβ oligomers in detergent-soluble brain homogenates (measured by sandwich ELISA) is shown. Data were obtained from APP/PS1 mice treated with vehicle (APP/PS1-V, n = 12) or GA (APP/PS1-GA, n = 12) for 6 months starting at 12 months of age. Data for B-E are presented as mean ± S.D. Statistical comparisons for B, C and E are between-groups, and for D, between-groups for each protein. **, p < 0.01; ***, p < 0.001 for APP/PS1-GA versus APP/PS1-V mice.