ABSTRACT
This chapter reviews transition metal ion dysregulation and oxidative stress in the pathogenesis of Alzheimer's disease. It focuses on the roles of metal ions in amyloidogenesis. The chapter assesses candidate neurochemical environments for their potential to induce β-sheet formation, aggregation, and chemical modifications of Alzheimer Aβ. The importance of metal ions in the brain is indicated by the fact that the brain contains high concentrations of metal ions relative to other tissues of the body. Zinc is a redox-inert metal ion that is crucial to the normal functioning of over 200 proteins and enzymes in their structural, catalytic, and regulatory roles. Copper is a redox-active essential trace metal ion required for a number of cellular enzymes including cytochrome c oxidase, copper/zinc sodium dodecyl sulfate, lysyl oxidase, and dopamine-β-monoxygenase. Iron is thought to play a crucial role in the maintenance of dopaminergic and GABAergic neurotransmission.
