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Science 22 March 2002:
Vol. 295. no. 5563, pp. 2264 - 2267
DOI: 10.1126/science.1067568
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Reports

Brain to Plasma Amyloid-beta Efflux: a Measure of Brain Amyloid Burden in a Mouse Model of Alzheimer's Disease

Ronald B. DeMattos,123* Kelly R. Bales,5* David J. Cummins,5 Steven M. Paul,56dagger David M. Holtzman1234dagger

The deposition of amyloid-beta (Abeta ) peptides into amyloid plaques precedes the cognitive dysfunction of Alzheimer's disease (AD) by years. Biomarkers indicative of brain amyloid burden could be useful for identifying individuals at high risk for developing AD. As in AD in humans, baseline plasma Abeta levels in a transgenic mouse model of AD did not correlate with brain amyloid burden. However, after peripheral administration of a monoclonal antibody to Abeta (m266), we observed a rapid increase in plasma Abeta and the magnitude of this increase was highly correlated with amyloid burden in the hippocampus and cortex. This method may be useful for quantifying brain amyloid burden in patients at risk for or those who have been diagnosed with AD.

1 Center for the Study of Nervous System Injury,
2 Alzheimer's Disease Research Center,
3 Department of Neurology,
4 Molecular Biology and Pharmacology, Washington University School of Medicine, 660 South Euclid Avenue, Box 8111, St. Louis, MO 63110, USA.
5 Neuroscience Discovery Research, Eli Lilly and Co., Lilly Research Laboratories, Indianapolis, IN 46285, USA.
6 Departments of Pharmacology, Toxicology, and Psychiatry, Indiana University School of Medicine, Indianapolis, IN 46285, USA.
*   These authors contributed equally to this work.

dagger    To whom correspondence should be addressed. E-mail: holtzman{at}neuro.wustl.edu (D.M.H.) or Paul_Steven_M{at}Lilly.com (S.M.P.)

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