Exploring the Step-Growth Polymerization Reaction Kinetics and Polydispersity of Amyloid Beta Aggregation

Abstract

The exact reaction pathway underlying amyloid beta aggregation kinetics remains a matter of debate, necessitating the development of better alternative models. Herein, to explore amyloid beta aggregation, a kinetic model based on the Aβ hypothesis is proposed. The model assumes step-growth Aβ polymerization reaction kinetics, unlike chain-growth polymerization, which has been a common practice to date. The model also explores the polydispersity of Aβ fibrils, which is generally lacking in the literature. The model parameters are tuned and rigorously validated with the reported experimental data available in the open literature. The validations are performed on different reported experimental data sets, including different fibril/monomer concentrations, lag time analysis, fibrils’ polydispersity index, and the plausibility of the tuned kinetic parameters. Comprehensive model dynamics and sensitivity analyses are also performed to examine the model’s robustness. It is envisaged that the proposed model may provide better insights into the aggregation pathways and aid in the development of drugs against Alzheimer’s disease.