Disruption of brain zinc homeostasis promotes the pathophysiological progress of Alzheimer's disease

Abstract

Zinc is abundant in the brain, where it plays an important role in synaptic plasticity and in learning; however, excessive zinc is toxic to neuronal cells, and dyshomeostasis of zinc in the brain is a contributing factor for Alzheimer's disease (AD). Deposition of zinc has been detected in senile plaques in the form of zinc-Aβ (β-amyloid) complexes. Recent studies have demonstrated that zinc exposure to the brain enhances β-amyloid precursor protein (APP) expression, amyloidogenic APP cleavage and plaque burden. Furthermore, alterations in zinc transporters, which are responsible for zinc homeostasis, occur in AD human brain and transgenic mouse models. These suggest that abnormal brain zinc homeostasis is involved in the pathophysiological progress of AD.