Alzheimer disease: evidence for a central pathogenic role of iron-mediated reactive oxygen species

Free radical formation, abnormalities in iron and copper distribution, and metal-catalyzed oxidation have all been noted in Alzheimer disease and are thought to play an important role in disease pathogenesis. Metal-catalyzed hydroxyl radical formation results in damage to every category of macromolecule found in the vulnerable neuronal populations in Alzheimer disease. In fact, redox activity resides within the cytosol of vulnerable neurons. Since oxidative damage represents one of the earliest pathological changes in Alzheimer disease, it is likely that aberrant redox activity is among the earliest changes in the transition to the disease state. In this review, we consider the wealth of evidence implicating a central role for metals in Alzheimer disease.