Effect of Metals on Kinetic Pathways of Amyloid-\b{eta} Aggregation

TL;DR

This paper reviews how metal ions like copper and zinc influence the amyloid-beta aggregation pathways, potentially leading to more toxic oligomeric species relevant to Alzheimer's disease.

Contribution

It synthesizes current literature to highlight the role of metal ions in altering amyloid-beta misfolding pathways and increasing neurotoxicity.

Findings

Metal ions modify amyloid-beta aggregation pathways.

Altered pathways may produce more toxic oligomers.

Metal presence correlates with increased neurotoxicity.

Abstract

Metal ions, including copper and zinc, have been implicated in the pathogenesis of Alzheimers disease through a variety of mechanisms including increased amyloid \b{eta} affinity and redox effects. Recent reports have demonstrated that the amyloid \b{eta} monomer does not necessarily travel through a definitive intermediary en-route to a stable amyloid fibril structure. Rather, amyloid \b{eta} misfolding may follow a variety of pathways resulting in a fibrillar end-product or a variety of oligomeric end-products with a diversity of structures and sizes. The presence of metal ions has been demonstrated to alter the kinetic pathway of the amyloid \b{eta} peptide which may lead to more toxic oligomeric end-products. In this work, we review the contemporary literature supporting the hypothesis that metal ions alter the reaction pathway of amyloid \b{eta} misfolding leading to more neurotoxic species.