Stochastic kinetic study of protein aggregation and molecular crowding effects of Aβ40 and Aβ42

Abstract

AbstractTwo isoforms of β‐amyloid peptides, Aβ40 and Aβ42, differ from each other only in the last two amino acids, IA, at the end of Aβ42. They, however, differ significantly in their ability in inducing Alzheimer's disease (AD). The rate curves of fibril growth of Aβ40 and Aβ42 and the effects of molecular crowding have been measured in in vitro experiments. These experimental curves, on the other hand, have been fitted in terms of rate constants for elementary reaction steps using rate equation approaches. Several sets of such rate parameters have been reported in the literature. Employing a recently developed stochastic kinetic method, implemented in a browser‐based simulator, popsim, we study to reveal the differences in the kinetic behaviors implied by these sets of rate parameters. In particular, the stochastic method is used to distinguish the kinetic behaviors between Aβ40 and Aβ42 isoforms. As a result, we make general comments on the usefulness of these sets of rate parameters.