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Aqueous Dissolution of Alzheimer's Disease Aβ Amyloid Deposits by Biometal Depletion

Year: 1999
Type: article
Abstract: Zn(II) and Cu(II) precipitate Abeta in vitro into insoluble aggregates that are dissolved by metal chelators. We now report evidence that these biometals also mediate the deposition of Abeta amyloid in Alzheimer's disease, since the solubilization of Abeta from post-mortem brain tissue was significantly increased by the presence of chelators, EGTA, N,N,N',N'-tetrakis(2-pyridyl-methyl) ethylene diamine, and bathocuproine. Efficient extraction of Abeta also required Mg(II) and Ca(II). The chelators were more effective in extracting Abeta from Alzheimer's disease brain tissue than age-matched controls, suggesting that metal ions differentiate the chemical architecture of amyloid in Alzheimer's disease. Agents that specifically chelate copper and zinc ions but preserve Mg(II) and Ca(II) may be of therapeutic value in Alzheimer's disease.
DOI: 10.1074/jbc.274.33.23223
Authors: Robert A. Cherny, Jacinta T. Legg, Catriona A. McLean, David P. Fairlie, Xudong Huang, Craig S. Atwood, Konrad Beyreuther, Rudolph E. Tanzi, Colin L. Masters, Ashley I. Bush
Institutions: Mental Health Research Institute, The University of Melbourne, The University of Queensland, Harvard University, Massachusetts General Hospital, Heidelberg University
Language: English
Subfield: Physiology
Field: Medicine
Open Access status: hybrid
Estimated APC paid: $3,430
OpenAlex ID: W2017550829
FWCI: 12.46
Cites: 23
Cited by: 482
Related to: 10