Chronic exposure to aluminum in drinking water increases inflammatory parameters selectively in the brain

J Neurosci Res. 2004 Feb 15;75(4):565-72. doi: 10.1002/jnr.10877.


A link between aluminum (Al) exposure and age-related neurological disorders has long been proposed. Although the exact mechanism by which the metal may influence disease processes is unknown, there is evidence that exposure to Al causes an increase in both oxidative stress and inflammatory events. These processes have also been suggested to play a role in Alzheimer's disease (AD), and exposure to the metal may contribute to the disorder by potentiating these events. Al lactate (0.01, 0.1, and 1 mM) in drinking water for 10 weeks increased inflammatory processes in the brains of mice. The lowest of these levels is in the range found to increase the prevalence of AD in regions where the concentrations of the metal are elevated in residential drinking water (Flaten [2001] Brain Res. Bull. 55:187-196). Nuclear factor-kappaB as well as tumor necrosis factor-alpha (TNF-alpha) and interleukin 1alpha (IL-1alpha) levels were increased in the brains of treated animals. The mRNA for TNF-alpha was also up-regulated following treatment. Enhancement of glial fibrillary acidic protein levels and reactive microglia was seen in the striatum of Al-treated animals. The level of amyloid beta (Abeta40) was not significantly altered in the brains of exposed animals. Insofar as no parallel changes were observed in the serum or liver of treated animals, the proinflammatory effects of the metal may be selective to the brain. Al exposure may not be sufficient to cause abnormal production of the principal component of senile plaques directly but does exacerbate underlying events associated with brain aging and thus could contribute to progression of neurodegeneration.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Aluminum Compounds / administration & dosage*
  • Animals
  • Brain / drug effects*
  • Brain / metabolism
  • Brain / pathology*
  • Cytokines / immunology
  • Cytokines / metabolism
  • Dose-Response Relationship, Drug
  • Drinking / physiology*
  • Environmental Exposure / adverse effects
  • Inflammation / chemically induced
  • Inflammation / immunology
  • Inflammation / metabolism
  • Lactates / administration & dosage*
  • Male
  • Mice
  • Mice, Inbred C3H
  • Mice, Inbred C57BL
  • Microglia / drug effects
  • Microglia / immunology
  • Microglia / metabolism
  • Water Supply / analysis*


  • Aluminum Compounds
  • Cytokines
  • Lactates
  • aluminum lactate