Apolipoprotein E and antioxidants have different mechanisms of inhibiting Alzheimer's beta-amyloid fibril formation in vitro.

摘要: We compared the mechanisms of apolipoprotein E- (apoE-) and antioxidant- (AO-) mediated inhibition beta-amyloid fibril (fA beta) formation in vitro, based on a nucleation-dependent polymerization model using fluorescence spectroscopy with thioflavin T. first applied kinetic plot to transform sigmoidal time-course curve fA beta from freshly prepared amyloid beta-peptides (A into straight line. Mathematical treatment this demonstrated that above-described is logistic provided us parameter t(1/2), time when rate maximum. t(1/2) beta-amyloids (1-42) (1-40) were 18.7 +/- 1.7 min 6.3 0.2 h, respectively (mean SD, n = 3) independent initial A concentration examined. Although apoE extended both betas dose-dependent manner, AO did not. On other hand, final amount formed was decreased by dose-dependently. then analyzed effect extension reaction beta, first-order model. proceed equilibrium dose-dependently formed. These results indicate inhibit vitro different suggest existence multiple pharmacological targets for prevention formation.