Redox-active metals, oxidative stress, and Alzheimer's disease pathology

Abstract

Considerable evidence is mounting that dyshomeostasis of the redox-active biometals, Cu and Fe, and oxidative stress contribute to the neuropathology of Alzheimer's disease (AD). Present data suggest that metals can interact directly with Aβ peptide, the principal component of β-amyloid that is one of the primary lesions in AD. The binding of metals to Aβ modulates several physiochemical properties of Aβ that are thought to be central to the pathogenicity of the peptide. First, we and others have shown that metals can promote the in vitro aggregation into tinctorial Aβ amyloid. Studies have confirmed that insoluble amyloid plaques in postmortem AD brain are abnormally enriched in Cu, Fe, and..