A molecular mechanism of aluminium-induced Alzheimer's disease?

An abundance of research has continued to link aluminium (Al) with Alzheime r's disease (AD) (Strong et al., J. Toxicol. Environ. Health 48 (1996) 599; Savory et al., J. Toxicol. Environ. Health 48 (1996) 615). Animals loaded with Al develop both symptoms and brain lesions that are similar to those f ound in AD. However, these animal models of Al intoxication are not represe ntative of human exposure to Al. They have not addressed the significance o f a truly chronic exposure to Al. If Al is a cause of AD it is effective at the level of our everyday exposure to the metal and AD will be one possibl e outcome of the life-long presence of a low, though burgeoning, brain Al b urden. Individual susceptibility to AD will be as much to do with differenc es in brain physiology as with changes in our everyday exposure to the meta l. There will be a chemical response and indeed biochemical/physiological r esponse in the brain to Al. The question is whether brain Al homeostasis co uld impact upon brain function. In reviewing the recent literature covering the neurotoxicity of Al and, in particular, of the known and probable mech anisms involved in brain Al homeostasis I have identified a mechanism throu gh which a truly chronic exposure to Al would bring about subtle and persis tent changes in neurotransmission which, in time, could instigate the casca de of events known collectively as AD. This mechanism involves the potentia tion of the activities of neurotransmitters by the action of AI-ATP at aden osine 5'-triphosphate (ATP) receptors in the brain. (C) 1999 Elsevier Scien ce Inc. All rights reserved.