Designed Amyloid Delta b Peptide Fibril - A Tool for High-Throughput Screening of Fibril Inhibitors

Amyloid peptide (A) fibril formation is widely believed to be the causative event of Alzheimers disease pathogenesis. Therapeutic approaches are therefore in development that target various sites in the production and aggregation of A. Herein we present a high-throughput screening tool to generate novel hit compounds that block A fibril formation. This tool is an application for our fibril model (A16-37Y20K22K24)4, which is a covalent assembly of four A fragments. With this tool, screening studies are complete within one hour, as opposed to days with native A1-40. A Z factor of 0.84 plus or minus 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 A fibril formation to test the validity of the system.