Aluminum in the diet and Alzheimer's disease: from current epidemiology to possible disease-modifying treatment

In recent years, interest in the potential role of metals in the pathogenesis of Alzheimer's disease (AD) has grown considerably. In particular, aluminum (Al) neurotoxicity was suggested after its discovery in the senile plaques and neurofibrillary tangles that represent the principal neuropathological hallmarks of AD. Al is omnipresent in everyday life and can enter the human body from several sources, most notably from drinking water and food consumption. The evidence supporting association from ingestion of Al from drinking water is somewhat stronger than for its ingestion from food. However, other elements present in drinking water, such as fluoride, copper, zinc, or iron could also have an effect on cognitive impairment or modify any Al neurotoxicity. Some epidemiological studies, but not all, suggested that silica could be protective against Al damage, because it reduces oral absorption of Al and/or enhances Al excretion. Some epidemiological investigations suggested an association between chronic exposure to Al and risk of AD, although this relationship falls short of all the criteria generally attributed to causation. Future studies need to be more rigorous to truly test the validity of previous findings and in doing so attempt to identify dose-response relationships between Al and AD risk which may provide new routes to disease-modifying treatment of AD or possibly some lifestyle modification, to supplement existing symptomatic approaches.