Effect of dietary zinc and copper on beta-amyloid precursor protein expression in the rat brain

The beta-amyloid precursor protein (APP) is the source of the amyloid beta-peptide that accumulates in the brain in Alzheimer's disease. Recently, APP has been shown to bind zinc and copper, and this binding has been suggested to control APP conformation and stability. In vitro studies show that zinc ions cause beta-amyloid protein to form plaques resembling the amyloid plaques found in the brains of patients with Alzheimer's disease. This suggests a role for zinc and/or copper in the neuropathogenesis of Alzheimer's disease. Male Sprague Dawley rats (100 +/- 10 g) were fed diets containing 5, 35, or 350 mu g zinc/g diet, and 1.5, 3 or 6 mu g copper/g diet for 6 weeks. Brain APP expression was determined by using Western blots. Proteins were separated on 8.5% SDS-PAGE, and the APP immunoreactive species were detected by using anti-Alzheimer precursor protein A4 clone 22C11. Alterations in dietary zinc and copper significantly (P < 0.05) affected ceruloplasmin, red blood cell and extracellular superoxide dismutase activities, and tissue mineral concentrations. Although brain zinc concentrations were 13% lower (P < 0.005) in animals fed low dietary Zinc than in animals fed high dietary zinc, and brain copper concentrations were 11% lower (P < 0.0001) in animals fed low dietary copper than in animals fed high dietary copper, there were no significant differences in the expression of APP among the different dietary treatments. Therefore, it seems that dietary zinc and copper do not affect APP expression in the rat brain. (C) 1997 Wiley-Liss, Inc.