Interaction between Aβ(1-42) and Aβ(1-40) in Alzheimer's β-amyloid fibril formation in vitro

We analyzed the interaction of two kinds of amyloid beta-peptides (A beta), i.e., A beta(1-42) and A beta(1-40), in the kinetics of beta-amyloid fibril (fA beta) formation in vitro, based on a nucleation-dependent polymerization model using fluorescence spectroscopy with thioflavin T, When 25 mu M A beta(1-42) was incubated with increasing concentrations of amyloidogenic A beta(1-40), the time to proceed to equilibrium was extended dose-dependently. A similar inhibitory effect was observed when 45 mu M A beta(1-40) was incubated with increasing concentrations of A beta(1-42). On the other hand, when 50 mu M of nonamyloidogenic AP(1-40) was incubated with AP(1-42) at a molar ratio of 10:1 or 5:1, ape (1-42) initiated fA beta formation from A beta(1-40). The lag time of the reaction shortened in a concentration-dependent manner, with AP(1-42). We next examined the seeding effect of fA beta formed from AP(1-42) (fA beta(1-42)) on nunamyloidogenic AP(1-40). When 50 mu M of nonamyloidogenic AP(1-40) was incubated with 10 or 20 mu g/mL (2.2 or 4.4 mu M) of fA beta(1-42), the fluorescence showed a sigmoidal increase, The lag time of the reaction was shortened by fA beta(1-42) in a concentration-dependent manner. However, the time to proceed to equilibrium was much longer than when an equal concentration of fA beta formed from A beta(1-40) (fA beta(1-40)) was added to AP(1-40). The fluorescence increased hyperbolically without a lag phase when 25 mu M AP(1-42) was incubated with 10 or 20 mu g/mL (2.3 or 4.6 mu M) of fA beta(1-40), and proceeded to equilibrium more rapidly than without fA beta(1-40). An electron microscopic study indicated that the morphology of fA beta formed is governed by the major component of fresh ap peptides in the reaction mixture, not by the morphology of preexistin fibrils. These results may indicate the central role of A beta(1-42) for fA beta deposition in vivo, among the different coexisting A beta species.