The Role of Copper in Alzheimer’s Disease Etiopathogenesis: An Updated Systematic Review

Background: Alzheimer’s disease (AD) is the most common cause of dementia and cognitive decline in the elderly. Although the etiology of AD is unknow, an increase in amyloid precursor protein (APP) leads to the toxic aggregation of Aβ plaques. Several factors, such as hypertension, diabetes, dyslipidemia, smoking, hormonal changes, and metal exposure, could increase the risk of developing AD. In this review, we will examine the role of copper (Cu) in the pathophysiology of AD, as well as the mechanisms involved in neurotoxicity and cognitive decline. Methods: This review was conducted in accordance with PRISMA guidelines. We performed a comprehensive literature analysis over the last ten years on AD and Cu. Only late-onset Alzheimer’s disease was considered; only studies on elderly people of both sexes were included. Results: A total of seven articles were picked for this review, three studies focused on non-ceruloplasmin-bound Copper (non-Cp-Cu) and four on ceruloplasmin-bound Copper (Cp-Cu). The results showed higher Cu concentrations in patients compared to healthy controls. Conclusions: Elevated concentrations of Cu may contribute to the progression of AD, potentially interacting with ATP7B mutations, oxidative stress (OS), and amyloid-β plaques. Future research is needed to provide more robust evidence and better characterize the relationship between AD and Cu.