Analysis of Amyloid Beta Aggregation Kinetics Using Sym-Triazine β-Sheet Inhibitors

AD (Alzheimers disease) is a progressive neurodegenerative disorder characterized by the cerebral accumulation of fibrillar amyloid-beta (A beta) aggregates. Here we present the electrochemistry of two novel sym-triazine derivatives (TAE-1, TAE-2) as modulators of A beta 142 aggregation in vitro. Incubation studies conducted at physiological conditions demonstrated strong inhibition of beta-sheet fibril formation. Uniquely, square-wave voltammetry indicated progressive changes in the surface-availability of amyloid-intercalated triazines for oxidation, mediated by competing peptide self-assembly. Time-resolved voltammetric analysis showed increasing anodic peak currents (=3-fold) and progressive shifts in redox potentials, measured over 24 h. The more potent aggregation modulator (TAE-2) showed prolonged association during the pre-nucleation states of A beta.