Abstract: A method of enhancing neprilysin activity and/or degrading amyloid-? peptides and/or oligomers in a subject with Alzheimer's disease is disclosed. The method comprises administering to the subject a compound selected from the group consisting of in a therapeutically effective amount to enhance the neprilysin activity and/or degrade the amyloid-? peptides and oligomers in the subject. Methods of improving symptoms and/or retarding progression of Alzheimer's disease and prophylactic treatment and/or treatment of Alzheimer's disease are also disclosed.

Abstract: Novel substrates for detection of activity of amyloid beta degrading enzyme, such as Neprilysin (NEP) and insulin degrading enzyme (IDE), associated with Alzheimer's disease, are provided. A quenched fluorogenic peptide substrate containing the first seven residues of the A?peptide plus a C-terminal Cys residue to detect neprilysin activity with a fluorophore attached to the C-terminal Cys and a quencher linked to the N-terminus of the peptide is disclosed. An assay system sensitive to endopeptidase activity of NEP and IDE, but insensitive to other A?-degrading enzymes is disclosed. Active compounds are identified by a cell-based assay system for high-throughput screening.