Stochastic Kinetic Study of Protein Aggregation and Molecular Crowding Effects of Ab40 and Ab42

TL;DR

This study uses a stochastic kinetic simulation to analyze and compare the aggregation behaviors of Ab40 and Ab42 peptides, providing insights into their differing roles in Alzheimer's disease.

Contribution

It introduces a stochastic kinetic approach with a browser-based simulator to differentiate the kinetic behaviors of Ab40 and Ab42 isoforms.

Findings

Stochastic simulations reveal differences in aggregation kinetics between Ab40 and Ab42.

The method assesses the usefulness of various rate parameter sets from literature.

Insights into molecular crowding effects on peptide fibril growth.

Abstract

Two isoforms of beta amyloid peptides, Ab40 and Ab42, differ from each other only in the last two amino acids, IA, at the end of Ab42. They, however, differ significantly in their ability in inducing Alzheimer's disease (AD). The rate curves of fibril growth of Ab40 and Ab42 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 Ab40 and Ab42 isoforms. As a result, we make general comments on the usefulness of these sets of rate parameters.