Role of amyloid-β–metal interactions in Alzheimer’s disease

Abstract

There is an evolving field of metallobiology that has begun to describe a key role for bioavailable metals (particularly copper, zinc and iron) in the pathogenesis of Alzheimer’s disease (AD). In particular, there is an apparent failure in metal ion homeostasis, potentially caused by a pathological mislocalization of the metals in the brain, which appears to be an obligatory step in both the precipitation and potentiation of the disease. A number of both preclinical and clinical studies have also provided a strong burden of proof that normalizing metal ion homeostasis represents a valid therapeutic target, and may indeed represent the first disease-modifying strategy for AD. The role of metals in the pathophysiology of AD will be discussed in this article.