Metal ion mediated aggregation of Alzheimer's disease peptides and proteins in solutions and at surfaces

Abstract

Although the pathogenesis of Alzheimer's disease (AD) is still unclear, abnormally high concentrations of metal ions, like copper, iron and zinc, were found in senile plaques of AD brain, which inspires extensive studies on the fundamental molecular interactions of metal ions with the pathogenic hallmarks, amyloid-β (Aβ) peptides and tau proteins, respectively forming senile plaques and neurofibrillary tangles (NFTs) in AD brains. Early works concern the concentration effect of the metal ions on Aβ and tau aggregation. Yet, it is obvious that the surrounding environment of the metal ions must also be considered, not just the metal ions as free accessible forms in the solution phase. The most important surrounding environment in vivo is a very large surface area from cell membranes and other macromolecular surfaces. These bio-interfaces make the kinetic pathways of metal ion mediated Aβ and tau aggregation radically different from those in the solution phase. To better understand the role of metal ions in AD peptide and protein aggregation, we summarize and discuss the recent achievements in the research of metal ion mediated Aβ and tau aggregation, particularly the corresponding mechanism differences between the solution phase and the surface environment. The metal ion chelation therapy for AD is also discussed from the point of the surface pool of metal ions.