Oxidation and Zinc In Models of Alzheimer's Disease

Ashley Bush, MD, PhD
Mental Health Researrch Institute of Victoria (Parkville, Victoria, Australia)
Year Awarded:
1999
Grant Duration:
April 1, 1999 to March 31, 2000
Disease:
Alzheimer's Disease
Award Amount:
$200,000
Grant Reference ID:
A1999049
Award Type:
Standard
Award Region:
US Northeastern

Oxidation and Zinc In Models of Alzheimer's Disease

Details


Metal ions play important roles in many biological processes and high concentrations of copper, zinc, and iron are found in the beta-amyloid (Ab) plaques characteristic of Alzheimer's disease. Dr. Bush has hypothesized that these metal ions may help hold the Ab subunits together as insoluble aggregates. In addition, Dr. Bush and his colleagues have also recently found that copper and iron ions cause the production of harmful hydrogen peroxide and reactive oxygen species from the Ab subunits, and this may contribute to neurotoxicity. The research team is now using a transgenic mouse model to examine whether zinc may be involved in hydrogen peroxide production and if zinc is abnormally distributed in the amyloid precursor protein (APP). Using the same model, he will determine if the Ab deposits are assembled by zinc and whether they can be resolubilized by zinc chelators.

Publications

Cherny, R.A., Atwood, C.S., Xilinas, M.E., Gray, D.N., Jones, W.D., McLean, C.A., Barnham, K.J., Volitakis, I., Fraser, F.W., Kim, Y.S., Huang, X., Goldstein, L.E., Moir R.E., Lim, J.T., Beyreuther, K., Zheng, H., Tanzi, R.E., Masters, C.L., and Bush, A.I., (2001) Treatment with a copper-zinc chelator markedly and rapidly inhibits B-amyloid accumulation in Alzheimer's disease transgenic mice. Neuron. 30(3):665-676. [Alzforum Recommended Paper]  

Atwood, C.S., Scarpa, R.C., Huang, X., Moir, R.D., Jones, W.D., Fairlie, D.P. Tanzi, R.E., and Bush, A.I. (2000) Characterization of copper interactions with alzheimer amyloid beta peptides: identification of an attomolar-affinity copper binding site on amyloid beta1-42. Journal of Neurochemistry. 75(3):1219-1233. [Alzforum Recommended Paper]  

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