Metal-associated amyloid-β species in Alzheimer's disease

Highly concentrated metals such as Cu, Zn, and Fe are found in amyloid-β (Aβ) plaques within the brain of Alzheimer's disease (AD). In vitro and in vivo studies have suggested that metal binding to Aβ could facilitate Aβ aggregation and generate reactive oxygen species (ROS), which could contribute to the neuropathogenesis of AD. The connection between metal–Aβ interaction/reactivity and AD development, however, has not been clearly revealed owing to the complexity of the disease. In this review, metal–Aβ interaction/reactivity and its relation to neurotoxicity are briefly discussed. Additionally, our review illustrates the recent progress of small molecules, capable of targeting metal–Aβ species and modulating their interaction/reactivity, which could offer a promising approach to interrogate their role in AD.

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► Generation and aggregation of amyloid-β, as well as its interaction/reactivity with metal ions in Alzheimer's disease.
► Involvement of metal ions associated with amyloid-β in the development of Alzheimer's disease.
► Current progress in the design of small molecules to target metal–amyloid-β species and modulate their interaction/reactivity.