Abstract
Oligomeric assemblies of the amyloid β-protein, Aβ, are thought to be the proximate neurotoxic agents in Alzheimer's disease (AD). Oligomer formation is a complex process that produces a polydisperse population of metastable structures. For this reason, formal structure-activity correlations, both in vitro and in vivo, have been difficult to accomplish. An analytical solution to this problem was provided by the application of a photochemical cross-linking method to the Aβ assembly system. This method, photo-induced cross-linking of unmodified proteins (PICUP), enabled the quantitative determination of the oligomer size distribution. We report here the integration of PICUP with SDS-PAGE and alkaline extraction procedures to create a method for the isolation of pure populations of oligomers of defined order. This method has been used successfully to provide material for formal structure-activity studies of Aβ oligomers.