Abstract

A major cause for cellular toxicity involved in the onset of several neurodegenerative diseases is the aberrant aggregation of proteins into toxic oligomers and eventually inert fibrils. In the case of Alzheimer’s disease, the main aggregating peptide is the amyloid β-peptide (Aβ). We aim to understand the thermodynamics and kinetics of the Aβ aggregation process, from isolated monomers into oligomers and under varying external conditions known to play a role during the development of Alzheimer’s disease, such as the presence of metal ions and lipid bilayers, or changes in pH. To this end, we use all-atom molecular dynamics simulations to explore the aggregation process and describe the aggregation pathways using transition networks calculated from the simulation data.