Fig. 1
Specificity of SAR255952 and humanized SAR228810 for soluble Aβ protofibrils and fibrillar forms but not low molecular weight Aβ or monomers. Synthetic Aβ42 was allowed to aggregate in aqueous saline buffer. Soluble, low molecular weight (LMW) Aβ complexes and Aβ monomers (red circles) were separated from higher order fibrillar aggregates (green triangles) by size exclusion chromatography. In ELISA apparent affinity determinations, SAR255952 demonstrates high affinity and strong preference for protofibrillar Aβ versus monomeric Aβ (a), unlike 3D6 (bapineuzumab) that equally binds to both Aβ conformations (b). Similar data were obtained with the humanized version SAR228810. In human AD cortical sections, SAR228810 specifically binds to compact amyloid deposits while 3D6, in addition, detects a large number of diffuse deposits (chromogenic stain panel c). This was confirmed with fluorescence labeling with SAR228810 binding to a large area around Congo red-positive core plaques, while 3D6 labeled in addition non-Congo red-positive deposits (diffuse deposits). Symbols and error bars indicate mean ± SEM from ELISA readings. Scale bars represent 300 μm in panel c and 1 μm in panel d