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

Author:

DeMattos Ronald B.123,Bales Kelly R.4,Cummins David J.4,Paul Steven M.45,Holtzman David M.1236

Affiliation:

1. Center for the Study of Nervous System Injury,

2. Alzheimer's Disease Research Center,

3. Department of Neurology,

4. Neuroscience Discovery Research, Eli Lilly and Co., Lilly Research Laboratories, Indianapolis, IN 46285, USA.

5. Departments of Pharmacology, Toxicology, and Psychiatry, Indiana University School of Medicine, Indianapolis, IN 46285, USA.

6. Molecular Biology and Pharmacology, Washington University School of Medicine, 660 South Euclid Avenue, Box 8111, St. Louis, MO 63110, USA.

Abstract

The deposition of amyloid-β (Aβ) 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 Aβ levels in a transgenic mouse model of AD did not correlate with brain amyloid burden. However, after peripheral administration of a monoclonal antibody to Aβ (m266), we observed a rapid increase in plasma Aβ 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.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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