Copper homeostasis and cuproptosis in Alzheimer's disease (Review).

Abstract

Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by neuroinflammation, synaptic dysfunction and neuronal loss. Research has revealed a connection between copper metabolism and the pathophysiology of AD, particularly through a newly identified form of copper‑dependent cell death referred to as cuproptosis. Cuproptosis is driven by the aggregation of lipoylated proteins and proteotoxic stress caused by excessive copper accumulation, leading to cellular demise, which is a key event in AD. While studies on copper levels in the brain in AD remain inconclusive, there is mounting evidence suggesting that an imbalance in copper homeostasis, particularly elevated labile copper levels, contributes to oxidative damage and neurodegeneration in patients with AD. The present review examines the role of cuproptosis in AD and discusses how targeting this pathway may provide novel therapeutic opportunities. By investigating the underlying mechanisms and potential clinical implications, the present review highlights that regulation of cuproptosis provides a promising approach for modulating disease progression and developing personalized treatment strategies for AD.