Effects of aluminum on the neurotoxicity of primary cultured neurons and on the aggregation of beta-amyloid protein

Recent epidemiological, neuropathological, and biochemical studies have sug gested a possible link between the neurotoxicity of aluminum and the pathog enesis of Alzheimer's disease. However, this relationship remains controver sial. To investigate detailed characteristics of neurotoxicity of aluminum, we used primary cultured neurons of rat cerebral cortex as an in vitro mod el system for the observation of morphological changes induced by chronic e xposure to aluminum. Although the exposure to aluminum chloride (10-100 muM ) for 1 week did not cause marked neuronal death, degeneration of neuritic processes and accumulation of tau protein and beta -amyloid protein appeare d after chronic exposure to 50 muM aluminum chloride for more than 3 weeks. We also investigated the polymerization of beta -amyloid protein in vitro using the immunoblotting technique. We thus found that aluminum induced con formational changes in beta -amyloid protein and enhanced its aggregation i n vitro. The aggregated beta -amyloid protein was dissolved by the addition of desferrioxamine, a chelator of aluminum. The aggregated beta -amyloid p rotein pre-incubated with aluminum formed fibrillar deposits on the surface of cultured neurons. (C) 2001 Elsevier Science Inc.