Résumé
Amyloid β peptide (Aβ) fibril formation is widely believed to be the causative event of Alzheimer’s disease pathogenesis. Therapeutic approaches are therefore in development that target various sites in the production and aggregation of Aβ. Herein we present a high-throughput screening tool to generate novel hit compounds that block Aβ fibril formation. This tool is an application for our fibril model (Aβ16–37Y20K22K24)4, which is a covalent assembly of four Aβ fragments. With this tool, screening studies are complete within one hour, as opposed to days with native Aβ1–40. A Z′ factor of 0.84±0.03 was determined for fibril formation and inhibition, followed by the reporter molecule thioflavin T. Herein we also describe the analysis of a broad range of reported inhibitors and non-inhibitors of Aβ fibril formation to test the validity of the system.