The anti-amyloidogenic effect is exerted against Alzheimer's β-amyloid fibrils in vitro by preferential and reversible binding of flavonoids to the amyloid fibril structure

How various anti-amyloidogenic compounds inhibit the formation of Alzheimer's beta-amyloid fibrils (fA beta) from amyloid beta-peptide (A beta) and destabilize fA beta remains poorly understood. Using spectrophotometry, spectrofluorometry, atomic force microscopy, sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and surface plasmon resonance (SPR), we investigated the anti-amyloidogenic effects of five flavonoids on fA beta in vitro. Oxidized flavonoids generally inhibited fA beta(1-40) formation significantly more potently than fresh compounds. Characterization of the novel fluorescence of myricetin (Myr) emitted at 575 nm with an excitation maximum at 430 nm in the presence of fA beta(1-40) revealed the specific binding of Myr to fA beta(1-40). By SPR analysis, distinct association and dissociation reactions of Myr with fA beta(1-40) were observed, in contrast to the very weak binding to the A beta monomer. A significant decrease in the rate of fibril extension was observed when > 0.5 mu M Myr was injected into the SPR experimental system. These findings suggest that flavonoids, especially Myr, exert an anti-amyloidogenic effect in vitro by preferentially and reversibly binding to the amyloid fibril structure of fA beta, rather than to A beta monomers.