Monomer Dynamics of Alzheimer Peptides and Kinetic Control of Early Aggregation in Alzheimer's Disease.

The rate of reconfiguration-or intramolecular diffusion-of monomeric Alzheimer (Aß) peptides is measured and, under conditions that aggregation is more likely, peptide diffusion slows down significantly, which allows bimolecular associations to be initiated. By using the method of Trp-Cys contact quenching, the rate of reconfiguration is observed to be about five times faster for Aß40 , which aggregates slowly, than that for Aß42 , which aggregates quickly. Furthermore, the rate of reconfiguration for Aß42 speeds up at higher pH, which slows aggregation, and in the presence of the aggregation inhibitor curcumin. The measured reconfiguration rates are able to predict the early aggregation behavior of the Aß peptide and provide a kinetic basis for why Aß42 is more prone to aggregation than Aß40 , despite a difference of only two amino acids.