Effect of dietary zinc and copper on ?-Amyloid precursor protein expression in the rat brain

Abstract

The β‐amyloid precursor protein (APP) is the source of the amyloid β‐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 β‐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 μg zinc/g diet, and 1.5, 3 or 6 μg 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. J. Trace Elem. Exp. Med. 10:249–258, 1997. © 1997 Wiley‐Liss, Inc. This article is a US Government work and, as such, is in the public domain in the United States of America.

Chronic Exposure to High Levels of Zinc or Copper has Little Effect on Brain Metal Homeostasis or Aβ Accumulation in Transgenic APP-C100 Mice

“…The high Zn diet of Davis (1997) also resulted in a trend towards decreased brain Cu levels, as was found in this study. The antagonistic affect of Zn on Cu levels is well known, and appears to be mediated primarily by competition for uptake at the level of the intestinal mucosa (Fischer et al 1984).…”

“…Previous metal feeding studies using rats have demonstrated increased brain Cu levels (11%) as a result of a high Cu diet, and increased brain Zn levels (13%) as a result of a high Zn diet (Davis 1997). The high Zn diet of Davis (1997) also resulted in a trend towards decreased brain Cu levels, as was found in this study.…”

High dietary arsenic exacerbates copper deprivation in rats

“…Panemangalore and Bebe reported that EC SOD was decreased only in copper deficiency (<1 g/g) or in rats fed copper marginal diets (approximately 2 g/g) containing high zinc concentrations (>60 g/g) [22]. Davis showed that there was no difference in EC SOD in rats fed low dietary zinc (5 g/g) when comparing groups fed 3 g copper/g to groups fed 1.5 g/g [23]. However, EC SOD was decreased in rats fed high-zinc diets low in copper [22,23].…”

“…Finding no copper effect on EC SOD was not surprising. Panemangalore and Bebe [22] and Davis [23] showed zinc status and the degree of copper deprivation markedly affects EC SOD. Panemangalore and Bebe reported that EC SOD was decreased only in copper deficiency (<1 g/g) or in rats fed copper marginal diets (approximately 2 g/g) containing high zinc concentrations (>60 g/g) [22].…”

Lead concentrations in elderly urban people related to blood pressure and mental performance: Results from a population-based study

“…Other genetic factors of interest would be expression of genes like the APP encoding for beta amyloids. Disturbed metabolism of metals, e.g., zinc and copper have been related to Alzheimer's disease [Davis, 1997] including decreased growth inhibitor factor (GIF) in astrocytes. GIF is recognized as metallothionein III (MT), a mainly zinc containing MT [Nordberg, 1998].…”