Session Speaker

Metals and Alzheimer's Disease. Potential Therapeutic Treatment with Metal Complexing Agents
José L. Domingo
Spain

Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by deposition of extracellular amyloid plaques, formation of intracellular neurofibrillary tangles and neuronal dysfunction in the brain. Nowadays, more than 25 million people in the world are affected by dementia, most suffering from AD. In both developed and developing nations, AD has a tremendous impact on the affected individuals, caregivers, and society. Potential AD treatments target many different pathways, and may one day be dosed in combination to increase efficacy and prevent cognitive deterioration in patients with AD. Recently, the "Metal Hypothesis of Alzheimer's Disease," has been proposed. This hypothesis stipulates that the neuropathogenic effects of Abeta (the principle component of beta-amyloid deposits) in AD are promoted by Abeta-metal interactions. It is based on a considerable body of previous evidence indicating a central role for biometals such as aluminum, copper, iron or zinc in many critical aspects of AD. In this review, the conclusions of a number of recent studies on metal chelator therapy as a potential treatment for AD are discussed. The effects of desferrioxamine and other chelating agents are reviewed. The role of the metal chelator clioquinol, which has been reported to reduce beta-amyloid plaques, presumably by chelation associated with copper and zinc, is also revised, whereas the potential role of silicon in AD is also discussed. Increasingly sophisticated pharmaceutical approaches are now being implemented to attenuate abnormal Abeta-metal interactions without causing systemic disturbance of essential metals.