Aluminum and copper interact in the promotion of oxidative but not inflammatory events: implications for Alzheimer's disease.

The etiology of Alzheimer's Disease (AD) is multifactorial. It has been suggested that transition metals such as copper (Cu) and iron (Fe) as well as aluminum (Al) may be involved in the pathogenesis of the disorder. While Cu and Fe are redox-active, Al only exists in the trivalent form and is redox-inert. We previously demonstrated that Al exposure causes an increase in inflammatory parameters in human glioblastoma T98G cells. In the present study we further demonstrate that co-exposure with Cu exacerbates the oxidative but not inflammatory effects of Al in this cell line. While Cu-induced reactive oxygen species (ROS) production was greatly enhanced in the presence of Al, TNF-alpha secretion induced by either metal was not further potentiated by simultaneous exposure to Al and Cu. Furthermore, exposure to both metals reduced the individual Al and Cu-induced activation of the immune-related transcription factor NF-kappaB. Therefore, while synergistic interaction between the two metals increases oxidative events, this does not lead to potentiation of Al-induced inflammation. Thus the ability of aluminum to promote inflammatory processes does not depend on an increase ROS production induced by interaction with transition metals.