title: Aluminum disruption of calcium homeostasis and signal transduction resembles change that occurs in aging and Alzheimer's disease.
abstract: Most humans living in industrialized societies are routinely exposed to bioavailable aluminum salts in the form of additives-in commercially-prepared foods, alum-clarified drinking water, certain pharmaceuticals, sunscreens, and other topical applications. Minute amounts of this aluminum are absorbed into the circulation. Trace aluminum levels cross the blood-brain barrier and progressively accumulate in large pyramidal neurons of the hippocampus, cortex, and other brain regions vulnerable in Alzheimer's disease. More aluminum enters the brain than leaves, resulting in a net increase in intraneuronal aluminum with advancing age. Aluminum is responsible for two main types of toxic damage in cells. As a pro-oxidant, aluminum causes oxidative damage both on its own and in synergy with iron. Aluminum also competes with, and substitutes for, essential metals-primarily Mg2+, iron and Ca2+ ions-in or on proteins and their co-factors. The author hypothesizes that intraneuronal aluminum interferes with Ca2+ metabolism in the aged brain and describes a way to test this hypothesis. This paper reviews: 1) major changes that occur in brain Ca2+ homeostasis and Ca2+ signaling, subtly with aging and more overtly in Alzheimer's disease; and 2) evidence from the scientific literature that aluminum causes these same changes in neurons.
authors.affiliation: UNSW Faculty of Medicine, University of New South Wales, St George Hospital Campus, Sydney, NSW, Australia.
authors.forename: J R
authors.initials: JR
authors.lastname: Walton
mesh_terms: D000375:Aging / Q000378:metabolism*; D000535:Aluminum / Q000378:metabolism*; D000544:Alzheimer Disease / Q000378:metabolism*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D006706:Homeostasis / Q000502:physiology*; D006801:Humans; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D000535:Aluminum; D002118:Calcium