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

Aberrant metal homeostasis may enhance the formation of reactive oxygen species and A beta oligomerization and may therefore be a contributing factor in Alzheimer's disease. This study investigated the effect of chronic high intake of dietary Zn or Cu on brain metal levels and the accumulation and solubility of A beta in vivo, using a transgenic mouse model that over expresses the C-terminal containing A beta fragment of human amyloid precursor protein but does not develop amyloid deposits. Exposure to chronic high Zn or Cu in the drinking water resulted in only slight elevations of the respective metals in the brain. Total A beta levels were unchanged although soluble A beta levels were slightly decreased, without visible plaque formation, enhanced gliosis, antioxidant upregulation or neuronal loss. This study indicates that brain metal levels are only marginally altered by long term oral exposure to extremely high Cu or Zn levels, and that this does not induce A beta-amyloid formation in human A beta expressing, amyloid-free mice, although this is sufficient to modulate A beta solubility in vivo.