Zinc and Alzheimer's disease: is there a direct link?

Zinc is an essential trace element in human biology, but is neurotoxic at high concentrations. Several studies show that zinc promotes aggregations of beta-amyloid protein, the main component of the senile plaques typically found in Alzheimer's disease brains. In other neurological disorders where neurons appear to be dying by apoptosis (gene-directed cell death), chelatable zinc accumulates in the perikarya of neurons before, or during degeneration. As there is evidence for apoptotic death of neurons in Alzheimer's disease, an involvement of zinc in this process needs to be investigated. Zinc interacts with enzymes and proteins, including transcription factors, which are critical for cell survival and could be linked to apoptotic processes. While controversial, some studies indicate that total tissue zinc is markedly reduced in several brain regions of Alzheimer's patients. At face value, it seems that a paradox exists between reports of a decrease in zinc in the Alzheimer's brain and the putative link to aberrant high zinc levels promoting plaque formation. An hypothesis to explain this inconsistency is presented. Neuropathological changes mediated by endogenous or exogenous stressors may be relevant factors affecting abnormal zinc metabolism. This paper reviews current investigations that suggest a role of zinc in the etiology of Alzheimer's disease.