Amyloid consists of beta-sheet polymers and is associated with disease and with functional assemblies Amyloid-forming proteins differ widely in native structures and sequences. We describe here how conformational preferences of non-polar amino acid residues can affect amyloid formation The most nonpolar residues promote either beta-strands (Val, Ile, Phe, and Cys. VIFC) or alpha-helices (Leu, Ala, and Met, LAM), while the most polar residues promote only alpha-helices. For 12 proteins associated with disease, the localizations of the amyloid core regions are known Eleven of these contain segments that are biased for VIFC, but essentially lack segments that are biased for LAM For the amyloid beta-peptide associated with Alzheimer's disease and an amyloidogenic fragment of the prion protein, observed effects of mutations support that VIFC bias favors formation of beta-sheet aggregates and arnyloid, while LAM bias prevents it VIFC and LAM profiles combine information on secondary structure propensities and polarity, and add a simple criterion to the prediction of amyloidogenic regions (C) 2010 Elsevier Inc All rights reserved