title: A molecular mechanism of aluminium-induced Alzheimer's disease?
abstract: An abundance of research has continued to link aluminium (Al) with Alzheimer'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 found in AD. However, these animal models of Al intoxication are not representative of human exposure to Al. They have not addressed the significance of 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 possible outcome of the life-long presence of a low, though burgeoning, brain Al burden. Individual susceptibility to AD will be as much to do with differences in brain physiology as with changes in our everyday exposure to the metal. There will be a chemical response and indeed biochemical/physiological response in the brain to Al. The question is whether brain Al homeostasis could impact upon brain function. In reviewing the recent literature covering the neurotoxicity of Al and, in particular, of the known and probable mechanisms involved in brain Al homeostasis I have identified a mechanism through which a truly chronic exposure to Al would bring about subtle and persistent changes in neurotransmission which, in time, could instigate the cascade of events known collectively as AD. This mechanism involves the potentiation of the activities of neurotransmitters by the action of Al-ATP at adenosine 5'-triphosphate (ATP) receptors in the brain.
authors.affiliation: Birchall Centre for Inorganic Chemistry and Materials Science, Department of Chemistry, Keele University, Staffordshire, UK. cha38@keele.ac.uk
authors.forename: C
authors.initials: C
authors.lastname: Exley
mesh_terms: D000535:Aluminum / Q000737:chemistry / Q000633:toxicity*; D000544:Alzheimer Disease / Q000139:chemically induced*; D000818:Animals; D002118:Calcium / Q000737:chemistry; D004195:Disease Models, Animal; D006801:Humans
chemical_list: D000535:Aluminum; D002118:Calcium