Fig. 2

In vivo-dosed crenezumab binds in a halo around amyloid plaques and to dystrophic neurites in PS2APP mice. In vivo-dosed crenezumab (200 mg/kg, i.v.) was visualized 7 days postdose with anti-hIgG-Alexa594 antibody (red), and plaques were stained with methoxy-X04 (blue). Representative epifluorescent images of plaque-associated halo of staining by crenezumab alone (c) and with plaques (d) in the cortex. Note the absence of staining in the control-injected (control IgG, gD) mice around plaques (a, b). In the amygdala (e–g), confocal z-stacked images show crenezumab binding was prominent around the core of the plaque but in regions not covered by microglia (e) (labeled with Iba1, green). This staining pattern was reminiscent of dystrophic neurites and was confirmed by co-staining of crenezumab (80 mg/kg, i.v., red) with markers of dystrophic neurites including BACE1 (green, f) and LAMP1 (green, g). Arrowheads indicate example regions of overlap. In vivo-dosed crenezumab (j, k, red, 120 mg/kg, IP) was localized to regions between methoxy-X04-labeled plaques (h, k, blue) and GFP-labeled dendrites (i, k, green) in the dentate gyrus of PS2APP-GFP (line M) mice (2 days postdose). Scale bar, 200 μm (a–d) and 50 μm (e–g)