Electrochemical studies of tau protein-iron interactions—Potential implications for Alzheimer’s Disease

[Display omitted] Tau, a family of microtubule-associated protein (MAP) that exists in six isoforms, is involved in the etiology of Alzheimer’s and upon hypophosphorylation gives rise to neurofibrillary tangles (NFTs) inside neurons. Here, we report the results of an electrochemical investigation into the interaction of Fe(II) and Fe(III) with surface-supported tau (Tau-410, 2N3R). Changes in current density and impedance changes were used to monitor metal-tau interactions and tau-tau interactions. Our detailed electrochemical studies of surface-supported tau protein is supported by X-ray photoelectron spectroscopy (XPS) and by measurement of interactions in solution by circular dichroism (CD) spectroscopy. In addition, we include the effects of tau phosphorylation on the interactions with Fe(II) and Fe(III). Our results clearly demonstrate that a) Fe(II) and Fe(III) bind to the tau protein, b) structural changes occur to tau upon metal binding, c) Fe(II) shows a more pronounced effect, d) phosphorylation affects the metal ion complexation and e) tau-tau interactions are mediated by Fe(II).