Inhibition of the formation of beta-amyloid fibrils (fA beta), as well as the destabilization of preformed fA beta in the CNS, would be attractive therapeutic targets for the treatment of Alzheimer's disease (AD). We reported previously that curcumin (Cur) inhibits fA beta formation from A beta and destabilizes preformed fA beta in vitro. Using fluorescence spectroscopic analysis with thioflavin T and electron microscopic studies, we examined the effects of ferulic acid (FA) on the formation, extension, and destabilization of fA beta at pH 7.5 at 37 degrees C in vitro. We next compared the anti-amyloidogenic activities of FA with Cur, rifampicin, and tetracycline. Ferulic acid dose-dependently inhibited fA beta formation from amyloid beta-peptide, as well as their extension. Moreover, it destabilized preformed fA beta s. The overall activity of the molecules examined was in the order of. Cur > FA > rifampicin = tetracycline. FA could be a key molecule for the development of therapeutics for AD. (c) 2005 Elsevier Inc. All rights reserved.