Overexpression of Alzheimer's disease amyloid-β opposes the age-dependent elevations of brain copper and iron

Abstract

Increased brain metal levels have been associated with normal aging and a variety of diseases, including Alzheimer's disease (AD). Copper and iron levels both show marked increases with age and may adversely interact with the amyloid-β (Aβ) peptide causing its aggregation and the production of neurotoxic hydrogen peroxide (H2O2), contributing to the pathogenesis of AD. Amyloid precursor protein (APP) possesses copper/zinc binding sites in its amino-terminal domain and in the Aβ domain. Here we demonstrate that overexpression of the carboxyl-terminal fragment of APP, containing Aβ, results in significantly reduced copper and iron levels in transgenic mouse brain, while overexpression of the A..