The potential role of aluminium in Alzheimer's disease

Aluminium is a trivalent cation that does not undergo redox changes. It has, nonetheless, been implicated in a variety of neurological disorders that have been associated with an increase in the formation of reactive oxygen species (ROS). The exact mechanism of aluminium toxicity is not known. However, accumulating evidence suggests that the metal can potentiate oxidative and inflammatory events, leading to tissue damage. A review of the epidemiological and clinical evidence linking aluminium to Alzheimer's disease (AD) is presented. The article discusses the role of aluminium in two mechanisms that have been linked to neurodegenerative disorders, including AD. Studies are summarized that describe how aluminium can potentiate iron-induced oxidative events. Involvement of aluminium in inflammatory responses, mediated by interleukins and other inflammatory cytokines, is also discussed. Although a direct relationship between aluminium and AD has not been clearly demonstrated, a detailed mechanistic basis for the hypothesis that aluminium may exacerbate events associated with AD is clearly emerging. The results discussed here have broad implications for the role played by aluminium and other metals in neurodegenerative diseases, and suggest that long-term exposure to supra-physiological amounts these metals should be avoided.