Extended Data Fig. 8: Aggregation kinetics in the presence of preformed seed fibrils at low concentration (2%).

Normalized ThT fluorescence as a function of time for reactions starting from 3 to 4 µM Aβ1-42 monomer and 2% (60 to 80 nM) Aβ1-42 fibrils in 20 mM HEPES/NaOH, 140 mM NaCl, 1 mM CaCl₂, pH 8.0 in the absence (black) and presence of a) ^chgantenerumab, b) m266, c) isotype control antibody (yellow), d) ^chaducanumab, or e) 3D6 at five concentrations as given by the colour code in panel A. The fitted curves in panels A-C allow only a variation of k₂, whereas the fitted curves in panels D and E allow only a variation of k₊. f). ThT fluorescence as a function of time for reactions starting from 3 μM Aβ1-42 in the absence (grey) or presence of 60 nM preformed seed fibrils made in the absence (black) or presence of 6 nM ^chaducanumab (green). The fits assume a constant value of k₊ and curve-specific values of k₂. The relative values of k₂ obtained are 1.0 (grey), 1.0 (black) and 0.67 (green). Thus, forming the seeds in the presence of ^chaducanumab leads to a 33% reduction in apparent k₂, very similar to what we observed with 6 nM ^chaducanumab in the non-seeded data (Extended Data Fig. 4a). We conclude that a substantial fraction of the inhibitory effect on secondary nucleation originates from interaction of the antibody with fibrillar aggregates.