Figure 6.

Effect of EpoD treatment on the Aβ production. (a1,a2) Quantitative western blots using 6E10 plus 82E1 antibodies in total proteins isolated from hippocampus of vehicle (n = 4) and EpoD mice (n = 7). APP/PS1^EpoD animals showed a significant reduction of monomeric Aβ levels as compared with the vehicle group (t test, **p < 0.01). For quantification, levels were referred to vehicle group. (b1,b2) Importantly, western blotting of isolated hippocampal synaptosomes using the same antibodies demonstrated a stronger reduction in Aβ content in this neuronal fraction of EpoD mice (t test, ***p < 0.001; n = 4 mice/group). (c1,c2) EpoD treatment also produced a strong reduction (***p < 0.001) on the soluble oligomeric Aβ accumulation. Aβ oligomers were assayed using OC or A11 dot blots. Equivalent S1 proteins from WT was used as negative controls. Protein loading was controlled using parallel dot-blots developed using ant-GAPDH (Supplemental Fig. S4). Direct effect of EpoD on BACE-1 (d) and γ-secretase (e1,e2) activities. No significant differences were observed (n = 6 independent experiments). Uncropped blots are shown in Supplementary Fig. S9.