Alzheimer’s disease has been intensely studied for decades, too much is still not known about molecular processes in the brain that cause it. Chemistry Professor Jianhan Chen says new insights from analytic theory and molecular simulation techniques offer a better understanding of amyloid fibril growth and brain pathology.
As senior author Chen notes, the “amyloid hypothesis” was promising – amyloid protein fibrils are a central feature in Alzheimer’s, Parkinson’s disease and other neurodegenerative diseases. “But the process is really difficult to study,” he says. Chen and first author Zhiguang Jia, a research scientist in Chen’s computational biophysics lab, explored how building-block peptides form fibrils. “We are really proud of this work because, to the best of our knowledge, for the first time we have described the comprehensive process of how fibril growth can happen. We illustrate that the effects of disease-causing mutations often arise from the cumulative effects of many small perturbations. A comprehensive description is absolutely critical to generate reliable and testable hypothesis,” he adds. Details of their multi-scale approach with many atomistic simulations are in Proceedings of the National Academy of Sciences.