Aluminum modulates brain amyloidosis through oxidative stress in APP transgenic mice

Epidemiological studies have implicated aluminum (Al) exposure in the pathogenesis of Alzheimer's disease (AD); however, other studies have failed to confirm these results. Oxidative stress is a feature of AD, and Al can exacerbate oxidative events. This biological property has been suggested as a possible mechanism by which this metal could influence the onset and/or evolution of the disease. To test this hypothesis, we fed transgenic mice that over express human amyloid precursor protein (Tg2576) with a diet enriched in Al and measured isoprostane levels, sensitive and specific markers of in vivo oxidative stress, as well as amyloid beta peptide formation and deposition. Here, we show an increase in brain isoprostane levels that correlated with increased amyloid beta levels and accelerated plaque deposition in Tg2576 mice but not in wildtype (WT) littermates fed with high dietary Al. Significantly, these in vivo effects of Al were reversed by vitamin E, as judged by a reduction of isoprostane production, amyloid beta levels, and plaque deposition. These results indicate that dietary Al can modulate in vivo AD-like amyloidosis in Tg2576 by increasing brain oxidative stress.