title: Zinc takes the center stage: its paradoxical role in Alzheimer's disease.
abstract: There is compelling evidence that the etiology of Alzheimer's disease (AD) involves characteristic amyloid-beta (Abeta) deposition, oxidative stress, and anomalous metal-Abeta protein interaction. New studies have implicated redox active metals such as copper, iron, and zinc as key mediating factors in the pathophysiology of Alzheimer's disease. There is also evidence that drugs with metal chelating properties could produce a significant reversal of amyloid-beta plaque deposition in vitro and in vivo. This paper reviews current observations on the etiologic role of zinc in AD. We also discuss the interactions of zinc and copper with Abeta, a factor that purportedly facilitates disease processes. Finally, we review the protective role of zinc against Abeta cytotoxicity and hypothesize how the apparent effect of zinc on AD pathology may be paradoxical, The Zinc Paradox. Indeed, complex pathologic stressors inherent to the Alzheimer's diseased brain dictate whether or not zinc will be neuroprotective or neurodegenerative. Further research on the zinc paradox in AD is needed in order to elucidate the exact role zinc plays in AD pathogenesis.
authors.affiliation: Department of Neurology, Molecular Neurogenetics Unit, Massachusetts General Hospital, Charlestown, MA 02129, USA. cuajungc@helix.mgh.harvard.edu
authors.forename: Math P
authors.initials: MP
authors.lastname: Cuajungco
authors.forename: Kyle Y
authors.initials: KY
authors.lastname: Fagét
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors / Q000378:metabolism*; D001921:Brain / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D002614:Chelating Agents / Q000494:pharmacology / Q000627:therapeutic use; D003300:Copper / Q000378:metabolism; D006801:Humans; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D015032:Zinc / Q000378:metabolism*
chemical_list: D016229:Amyloid beta-Peptides; D002614:Chelating Agents; D003300:Copper; D015032:Zinc