Extended Data Fig. 6: Effects of the antibodies on the aggregation kinetics of Aβ1-42 in CSF.
From: Kinetic fingerprints differentiate the mechanisms of action of anti-Aβ antibodies
ThT fluorescence as a function of time for reactions starting from 6 µM Aβ1-42 in 66% CSF, 20 mM HEPES/NaOH, 140 mM NaCl, 1 mM CaCl2, pH 8.0 in the absence and presence of chaducanumab (a), m266 (b), 3D6 (c) or chgantenerumab (d). The colour codes for the antibody concentrations are given in nM in each panel. The left column shows data obtained in the presence of 30% preformed seeds, with linear fits, and the following three columns show non-seeded data fitted three times with the selective variation of one rate constant in each column. For chaducanumab, the heavy seeded data rule out an effect on k+, and we can identify a reduction in k2 as the model which best fits the chaducanumab data in CSF; this is verified using light seeding in CSF (Extended Data Fig. 7). Likewise, for m266 the heavy seeded data rule out an effect on k+, and we can identify a reduction in kn as the model which best fits the m266 data in CSF. For 3D6 as well as chgantenerumab, the seeded data show an effect on k+, which indeed explains also the non-seeded data in CSF. Note that the x-axis covers 2.2, 6 or 8 h depending on the magnitude of the effect of each antibody.
