Extended Data Fig. 3: Aggregation kinetics data of Aβ1-42 in the absence and presence of antibodies.
From: Kinetic fingerprints differentiate the mechanisms of action of anti-Aβ antibodies
All panels show data acquired using recombinant Aβ1-42 at 37 °C under quiescent conditions in 20 mM HEPES/NaOH, 140 mM NaCl, 1 mM CaCl2, pH 8.0 in PEGylated plates. (a–c) Normalized data with chaducanumab (A,B) and isotype control (C). The same data are shown in non-normalized form in panels (d, e) and (g), respectively. Panels (f, h, i) show the same data as shown in Fig. 1, and in addition panel H includes data at 500–2000 nM 3D6. The fitted lines in panel A are with reduced values of k2. The fits in panel B, to normalized data in the absence and presence 250–1000 nM chaducanumab, allow for a decrease in k2 and an increase in kn. We note that at very high concentrations (>500 nM), which are unlikely to be realized in vivo, chaducanumab accelerates the bulk Aβ42 aggregation process by increasing the primary nucleation rate. Indeed, the data at 250–1000 nM chaducanumab are best fitted assuming that the effect on k2 is combined with an increase in kn (Extended Data Fig. 4). Interestingly, at high concentrations of each antibody, the ThT intensity is significantly reduced, which for m266 and 3D6, is found to be related to a substantial concentration of Aβ1-42 remaining in solution (Extended Data Fig. 5), implying the possibility of monomer binding which we assess directly in solution (Fig. 3).
