Reactive oxygen species may cause amyloid beta aggregation by free radical polymerization

Abstract

Alzheimer's disease (AD), the most common form of dementia, is closely related to the overproduction of reactive oxygen species (ROS). A kinetic model based on free radical polymerization of amyloid beta (Aβ) utilizing ROS as an initiator is proposed. Kinetic parameters involved in the model are tuned with the reported experimental data on fibril molecular weight. The tuned model is used to simulate time evolution of fibril length and polydispersity of Aβ aggregates. The simulated values are compared with the reported experimental values for these fibril properties. A good agreement is observed between the model simulated fibril properties and the reported experimental data. This supports the hypothesis of ROS as the cause of Aβ aggregation using the free radical polymerization. The proposed model is also able to predict the sigmoidal growth of fibrils at different set of parameter values. Sensitivity analysis has been performed to check the reliability of the proposed model. It is envisaged that the proposed model will be helpful to elucidate ROS‐based therapeutic strategies for AD treatment in near future.