Fig. 5

Crenezumab binding to the hippocampal mossy fibers is Aβ dependent. Representative epifluorescent images of in vivo-dosed crenezumab (80 mg/kg) binding to the mossy fibers (a) of PS2APP mice (arrows). Immunostaining for BACE1 shows strong binding in the mossy fibers (b) that overlap with crenezumab staining (c, merge). Scale bar = 50 μm. In vivo-dosed crenezumab (80 mg/kg) staining to the mossy fibers in the PS2APP/BACE1^WT/WT mice (d) was nearly completely absent in PS2APP/BACE1^KO/KO (e) compared with Ntg/BACE1^WT/WT (f) mice. Scale bar, 200 μm. g Significant differences in mossy fiber binding were found between the groups (ANOVA: F_2,8 = 29.16, p < 0.001) n = 3–4/group. ANOVA followed by Tukey’s multiple comparison test. ***p < 0.001 versus all others. h Western blots of full-length/soluble APP and Aβ (detected by 4G8 and 6E10) and α/β–C-terminal fragment (detected by SIG-39152) from soluble hippocampal TBS homogenates from PS2APP/BACE1^WT/WT, PS2APP/BACE1^KO/KO, and Ntg/BACE1^WT/WT mice. β-Tubulin (Tuj1) was used as a loading control. M, molecular weight marker