The metallobiology of Alzheimer's disease

Abstract

The cause of Alzheimer's disease (AD) is closely related to the aggregation of a normal protein, β-amyloid (Aβ), within the neocortex. Recently, evidence has been gathered to suggest that Aβ precipitation and toxicity in AD are caused by abnormal interactions with neocortical metal ions, especially Zn, Cu and Fe. However, Aβ might also participate in normal metal-ion homeostasis. An inevitable, age-dependent rise in brain Cu and Fe might hypermetallate the Aβ peptide, causing the catalysis of H2O2 production that mediates the toxicity and auto-oxidation of Aβ. The greater incidence of AD in females could be due to greater constitutive activity of the synaptic Zn transporter ZnT3, and attenua..