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.