Brain Aging and Trace Elements in Human: Clues into the Pathogenesis of Alzheimer's Disease

The relationship between three trace elements (aluminium, zinc and selenium) and Alzheimer's disease is reviewed. Several arguments are discussed towards the role of these trace elements in the formation of the cardinal histologic lesions found in the brain, respectively, neurofibrillary tangles with aluminium, senile plaques and amyloid deposits with zinc, and lipofuschin with selenium. Aluminium may exert its primary action in the olfactory bulb. The neurotoxicity of aluminium is secondary to an alteration of calcium homeostasis, and/or of chromatin in the nucleus of neurons. Hippocampal zinc changes may result in an alteration in the activity of excitatory amino-acids and/or Cu-Zn superoxide dismutase. Finally, a decrease in brain selenium and glutathione peroxidase could lead to the deleterious effect of an increased production of free radicals. However, none of these mechanisms are mutually exclusive and the complex process of brain aging is in fact the result of multiple events.