The invention is based on the discovery that the presence of a discordant helix in a protein or peptide is predictive of that protein or peptide's ability to form amyloid. The invention includes methods for detecting discordant helices and methods of screening for compounds that stabilize the &agr;-helix of a discordant helix-containing polypeptide. Compounds discovered using these methods are useful for treating or preventing disorders in which amyloid is produced. Such disorders include Alzheimer's disease and prion-associated disorders.