Fibrillogenesis of Alzheimer Aβ peptides studied by fluorescence energy transfer

Pathogenesis of Alzheimer’s disease is associated with the polymerization of the Aβ peptide into fibrils that accumulate to form plaques. One strategy for therapy is the targeting of inhibitors against fibrillogenesis; however, prior to the formulation of specific tactics, a thorough understanding of the polymerization mechanism is essential. We have applied the principle of fluorescence energy transfer to monitor fibrillogenesis. In theory, this method is capable of measuring fibrillogenesis at physiological concentrations of peptide. Using this assay, we have determined that: fibril formation by Aβ(9-25) is reversible and cooperative, there are two imidazole-carboxylate salt bridges per monomer, monomers are in free exchange with fibrils, and the exchange process displays measurable kinetics.