The toxicology of aluminum in the brain: a review

Aluminum is environmentally ubiquitous, providing human exposure. Usual human exposure is primarily dietary. The potential for significant Al absorption from the nasal cavity and direct distribution into the brain should be further investigated. Decreased renal function increases human risk of Al-induced accumulation and toxicity. Brain Al entry from blood may involve transferrin-receptor mediated endocytosis and a more rapid process transporting small molecular weight Al species. There appears to be Al efflux from the brain, probably as Al citrate. There is prolonged retention of a fraction of Al that enters the brain, suggesting the potential for accumulation with repeated exposure. Al is a neurotoxicant in animals and humans. It has been implicated in the etiology of sporadic Alzheimer's disease (AD) and other neurodegenerative disorders, although this is highly controversial. This controversy has not been resolved by epidemiological studies, as only some found a small association between increased incidence of dementia and drinking water Al concentration. Studies of brain Al in AD have not produced consistent findings and have not resolved the controversy. Injections of Al to animals produce behavioral, neuropathological and neurochemical changes that partially model AD. Aluminum has the ability to produce neurotoxicity by many mechanisms. Excess, insoluble amyloid beta protein (A beta) contributes to AD. Aluminum promotes formation and accumulation of insoluble A beta and hyperphosphorylated tau. To some extent, Al mimics the deficit of cortical cholinergic neurotransmission seen in AD. Al increases Fe-induced oxidative injury. The toxicity of Al to plants, aquatic life and humans may share common mechanisms, including disruption of the inositol phosphate system and Ca regulation. Facilitation of Fe-induced oxidative injury and disruption of basic cell processes may mediate primary molecular mechanisms of Al-induced neurotoxicity. Avoidance of Al exposure, when practical, seems prudent.