Zinc is an essential trace element in human biology, but is neurotoxic
at high concentrations. Several studies show that zinc promotes aggre
gation of beta-amyloid protein, the main component of the senile plaqu
es typically found in Alzheimer's disease brains. In other neurologica
l disorders where neurons appear to be dying by apoptosis (gene-direct
ed cell death), chelatable zinc accumulates in the perikarya of neuron
s before, or during degeneration. As there is evidence for apoptotic d
eath of neurons in Alzheimer's disease, an involvement of zinc in this
process needs to be investigated. Zinc interacts with enzymes and pro
teins, including transcription factors, which are critical for cell su
rvival 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 Al
zheimer's brain and the putative link to aberrant high zinc levels pro
moting plaque formation. An hypothesis to explain this inconsistency i
s presented. Neuropathological changes mediated by endogenous or exoge
nous stressors may be relevant factors affecting abnormal zinc metabol
ism. This paper reviews current investigations that suggest a role of
zinc in the etiology of Alzheimer's disease. (C) 1997 Elsevier Science
B.V.