The Design of Metal Complexes to Target the Amyloid‐β Peptide in Alzheimer's Disease

Abstract Alzheimer's disease (AD) is a devastating neurological disorder where a pathological hallmark is the occurrence of amyloid‐β (Aβ) peptide deposits, also known as Aβ plaques. The Aβ peptide is known to self‐associate and aggregate in solution, a phenomenon that is accelerated in the presence of metal ions, in particular Fe, Cu, and Zn. Furthermore, these micronutrient metals are found in elevated concentration within Aβ plaques, relative to nearby healthy tissues. Therapeutic approaches have sought to exploit this metalloprotein nature of Aβ by designing metal complexes that can target either the soluble peptide or its pathological aggregate species. Overall, complexes of 27 different metals have been designed to target the Aβ that can detect its presence in biological samples, modulate its aggregation, and/or prevent its neurotoxic activity. This article summarizes these compounds, and the advances made for complexes of each metal.