WT-TTR and M-TTR display
strong inhibition of primary nucleation
in Aβ40 aggregation. (a–f) Time courses of
fibril formation by 5.0 μM Aβ40 in the presence
of WT-TTR (a–c) and M-TTR (d–f) at the indicated concentrations
(m.e.). The solid lines are fits of the kinetic profiles by a model
in which secondary nucleation (a, d), elongation (b, e), or primary
nucleation (c, f) is inhibited by TTRs. (g) Incubation of 20, 30,
and 50 μM WT-TTR and M-TTR under the same conditions in the
absence of Aβ40. (h) Change in the effective rate
constants of primary nucleation in Aβ40 aggregation,
as derived from (e) and (f), shown with increasing concentrations
of WT-TTR (green) and M-TTR (black). Error bars are s.d. of the rates
obtained from individual fitting of the repeats. The traces in (a)–(f)
show the average traces of those repeats.