COMPUTATIONAL PREDICTIONS FOR THE NUCLEATION MASS AND LAG TIMES INVOLVED IN Aβ42 PEPTIDE AGGREGATION

The aggregates of amyloid-beta (A beta) peptide are the primary neurotoxic species in the brains of Alzheimer's patients. We study the molecular-level dynamics of this process employing chemical kinetic simulations by dissecting the aggregation pathway into pre-nucleation, post-nucleation and protofibril elongation stages. Here, we discuss how our earlier identified rate constants for protofibril elongation were incorporated into a simplified simulation of the complete aggregation process to understand the lag-times in the sigmoidal fibril growth curves of fibril formation. We also present some initial findings on the rate constants and possible hypotheses on the nucleation mass involved in the pre-nucleation stage.