Fig. 6
In vivo-dosed crenezumab binds to (o)ligomeric Aβ, not to (mo)nomeric Aβ, in the hippocampal mossy fiber tract. Plasma and cerebellum PK levels 6 h after the final day of dosing (100 mg/kg daily for 5 d) with an anti-moAβ (n = 3) or 5 days after a single injection of control IgG (anti-gD 40 mg/kg, n = 4) or crenezumab (80 mg/kg, n = 4) in PS2APP mice. ANOVA found a significant difference in plasma PK levels (a) (F2,8 = 86.90, p < 0.0001) but not in the cerebellum (b; not significant [NS]). Quantification (c) and representative epifluorescent images (d–f) of mossy fiber binding by crenezumab but not by control IgG or moAβ antibodies. ANOVA found a significant difference in binding (F2,8 = 26.84, p < 0.001). Representative images of ex vivo oAβ staining in the mossy fibers (arrows) of PS2APP mice (g), but not in Ntg mice (h), using an anti-oAβ antibody (mab-M). Scale bar, 50 μm. ANOVA followed by Tukey’s multiple comparison test: *p < 0.05, ***p < 0.001, ****p < 0.0001 as indicated or to control IgG