Potent anti-amyloidogenic and fibril-destabilizing effects of polyphenols in vitro:: implications for the prevention and therapeutics of Alzheimer's disease

Cerebral deposition of amyloid beta-peptide (Abeta) in the brain is an invariant feature of Alzheimer's disease (AD). A consistent protective effect of wine consumption on AD has been documented by epidemiological studies. In the present study, we used fluorescence spectroscopy with thioflavin T and electron microscopy to examine the effects of wine-related polyphenols ( myricetin, morin, quercetin, kaempferol (+)-catechin and (-)- epicatechin) on the formation, extension, and destabilization of beta-amyloid fibrils (fAbeta) at pH 7.5 at 37 degreesC in vitro. All examined polyphenols dose-dependently inhibited formation of fAbeta from fresh Abeta(1 - 40) and Abeta(1 - 42), as well as their extension. Moreover, these polyphenols dose-dependently destabilized preformed fAbetas. The overall activity of the molecules examined was in the order of: myricetin = morin = quercetin > kaempferol > (+)- catechin = ( -)- epicatechin. The effective concentrations (EC50) of myricetin, morin and quercetin for the formation, extension and destabilization of fAbetas were in the order of 0.1-1 muM. In cell culture experiments, myricetin-treated fAbeta were suggested to be less toxic than intact fAbeta, as demonstrated by 3-[4,5-dimethylthiazol-2-yl]-2,5- diphenyltetrazolium bromide assay. Although the mechanisms by which these polyphenols inhibit fAb formation from Abeta, and destabilize pre-formed fAbeta in vitro are still unclear, polyphenols could be a key molecule for the development of preventives and therapeutics for AD.