Alzheimer’s disease, transmissible spongiform encephalopathies and Parkinson’s disease are associated with amyloid fibrils sharing a common cross beta-sheet structure. Recent reports suggest that soluble oligomers which form early in the aggregation process are also cytotoxic. Therefore understanding the early steps of aggregation at an atomic detail might be crucial for the rational design of anti-amyloid agents. In this study, we coupled the Activation-Relaxation Technique and a generic free energy model to determine the energy landcape and aggregation pathways of several Alzheimer’s disease peptides. We show that the assembly is much more complex than previously thought.
LBT – IBPC – Université Paris VII