The metallobiology of Alzheimer's disease — Bush, 2003

Alzheimer's disease (AD) is caused by an abnormal protein called -amyloid (A) aggregating inside the neocortex. Current research suggests that aberrant interactions with neocortical metal ions, particularly Zn, Cu, and Fe, are to blame for A precipitation and toxicity in AD. A may, however, also take part in typical metal-ion homeostasis. The A peptide may become hypermetallated due to an unavoidable, age-dependent increase in brain Cu and Fe, catalyzing the creation of H2O2, which mediates the toxicity and auto-oxidation of A. The increased constitutive activity of the synaptic Zn transporter ZnT3 may be the cause of the higher prevalence of AD in females, and the rodent counterpart of A's reduced metal ion binding may be the reason these animals do not develop Alzheimer's disease. In vitro, substances that prevent metal-ion binding to A dissolve brain deposits. Clioquinol is one such substance that suppresses A deposition in the Tg2576 mouse model for AD and may have clinical applications. Several degenerative diseases where metal-ion-protein interactions have been linked may benefit from these understandings.

Ashley I. Bush, The metallobiology of Alzheimer's disease, Trends in Neurosciences, Volume 26, Issue 4, 2003, Pages 207-214, ISSN 0166-2236, https://doi.org/10.1016/S0166-2236(03)00067-5.