Anti-amyloidogenic activity of tannic acid and its activity to destabilize Alzheimer's β-amyloid fibrils in vitro

AbstractInhibition of the accumulation of amyloid β-peptide (Aβ) and the formation of β-amyloid fibrils (fAβ) from Aβ, as well as the destabilization of preformed fAβ in the CNS would be attractive therapeutic targets for the treatment of Alzheimer's disease (AD). We previously reported that nordihydroguaiaretic acid (NDGA) and wine-related polyphenols inhibit fAβ formation from Aβ(1–40) and Aβ(1–42) as well as destabilizing preformed fAβ(1–40) and fAβ(1–42) dose-dependently in vitro. Using fluorescence spectroscopic analysis with thioflavin T and electron microscopic studies, we examined the effects of polymeric polyphenol, tannic acid (TA) on the formation, extension, and destabilization of fAβ(1–40) and fAβ(1–42) at pH 7.5 at 37 °C in vitro. We next compared the anti-amyloidogenic activities of TA with myricetin, rifampicin, tetracycline, and NDGA. TA dose-dependently inhibited fAβ formation from Aβ(1–40) and Aβ(1–42), as well as their extension. Moreover, it dose-dependently destabilized preformed fAβs. The effective concentrations (EC50) of TA for the formation, extension and destabilization of fAβs were in the order of 0–0.1 μM. Although the mechanism by which TA inhibits fAβ formation from Aβ as well as destabilizes preformed fAβ in vitro is still unclear, it could be a key molecule for the development of therapeutics for AD