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 b peptide formation and deposition. Here, we show an increase in brain isoprostane levels that correlated with increased amyloid b levels and accelerated plaque deposition in Tg2576 mice but not in wild-type (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 b levels, and plaque deposition. These results indicate that dietary Al can modulate in vivo AD-like amyloidosis in Tg2576 by increasing brain oxidative stress.
Praticò
Domenico
D
Center for Experimental Therapeutics and Department of Pharmacology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA. domenico@spirit.gcrc.upenn.edu
Uryu
Kunihiro
K
Sung
Syan
S
Tang
Sei
S
Trojanowski
John Q
JQ
Lee
Virginia M-Y
VM
D000284:Administration, Oral; D000535:Aluminum / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000633:toxicity*; D016229:Amyloid beta-Peptides / Q000096:biosynthesis; D016564:Amyloid beta-Protein Precursor / Q000235:genetics*; D000686:Amyloidosis / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001921:Brain; D001927:Brain Diseases / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D015227:Lipid Peroxidation / Q000187:drug effects; D051379:Mice; D008822:Mice, Transgenic; D008954:Models, Biological; D018384:Oxidative Stress / Q000187:drug effects; D010446:Peptide Fragments / Q000096:biosynthesis; D014810:Vitamin E / Q000494:pharmacology
D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D000975:Antioxidants; D010446:Peptide Fragments; D014810:Vitamin E; D000535:Aluminum