Metal-catalyzed oxidation and free radical formation are potent mediators of cellular injury to every category of macromolecule found in vulnerable neuronal populations and are thought to play an early and central role in Alzheimer disease (AD) pathogenesis. While metal-binding sites are present in proteins that accumulate in AD, metal-associated redox activity is primarily noted with nucleic acids, specifically with cytoplasmic RNA. Iron dyshomeostasis in AD is thought to arise from haem breakdown and mitochondrial turnover, and a reduction in microtubule density in vulnerable neurons increases redox-active metals, initiating a cascade of events culminating in characteristic pathologic features. Increased understanding of these early changes may be translated into more effective therapeutic modalities for AD than those currently in use.