Elevated Levels of Copper in Amyloid Plaques Associated with Neurodegeneration in Mouse Models of Alzheimer's Disease

Findings Published in Biomedical Spectroscopy and Imaging Suggest Excess Copper May Be Neurotoxic or at Least Indicative of Early Abnormality

August 22, 2013

IOS Press, publisher of Biomedical Spectroscopy and Imaging, issued the following news release on Wednesday, August 21. The work was completed at the National Synchrotron Light Source at the U.S. Department of Energy's Brookhaven National Laboratory, led by Brookhaven biophysical chemist Lisa Miller. 

For more information about Brookhaven's role, contact Chelsea Whyte, cwhyte@bnl.gov, 631-344-8671, or Peter Genzer, genzer@bnl.gov, 631-344-3174.

IOS Press Media Contact: Esther Mateike, e.mateika@iospress.nl, +31 20 688 3355

Amsterdam, NL, 21 August 2013 – Metals such as iron, copper, and zinc are important for many biological processes. In recent years, studies have shown that these nutritionally-essential metals are elevated in human Alzheimer's disease (AD) brains and some animal models of AD. Scientists are now exploring whether these metals are causing the neurodegeneration seen in AD or are indicative of other ongoing pathologic processes. 

In a new study, investigators used synchrotron x-ray fluorescence microscopy to image metal ions in the brain, focusing on the amyloid plaques that are the hallmark of AD.  They found that, in two AD mouse models that exhibit neurodegeneration, the plaques contained about 25% more copper than an AD mouse model that shows little neurodegeneration. Looking at other metals, they found that none of the mouse models had significant increases in iron and very little increases in zinc. Metal content was not related to the age of the plaque. The study is reported in the current issue of Biomedical Spectroscopy and Imaging. 

"Since excess copper should not be 'free' in the brain to bind to the plaques, these data suggest that the cellular control of copper is altered in AD, which may lead to toxic reactions between free copper ions and neurons," comments lead investigator Lisa M. Miller, PhD, a biophysical chemist in the Photon Sciences Directorate at Brookhaven National Laboratory. In previous work, Dr. Miller's group found very high levels of copper in human AD plaques. 

Since elevated iron in the AD brain is well documented in both human brains and AD mouse models, the researchers measured iron content in the cortex of all three mouse models. They found that iron content was doubled in all AD mouse model cortices compared to controls, whether or not the models showed neurodegeneration. Upon further investigation, spectroscopic data revealed that the excess iron was present in the ferric (oxidized) state and consistent with the iron storage protein ferritin. "The increase in iron may be a reflection of changes in metalloprotein content and metal storage within the brain that is not well understood," says Dr. Miller.

Nevertheless, since iron in ferromagnetic and detectable through MRI, Dr. Miller suggests that in the future iron may be used as a biomarker for AD at early stages of disease, even before plaques are formed.  

This work was completed at the National Synchrotron Light Source, beamlines X27A and X3B at Brookhaven National Laboratory.

Notes For Editors

"Elevated copper in the amyloid plaques and iron in the cortex are observed in mouse models of Alzheimer's disease that exhibit neurodegeneration," by Megan W. Bourassa, Andreana C. Leskovjan, Ryan V. Tappero, Erik R. Farquhar, Carol A. Colton, William E. Van Nostrand, and Lisa M. Miller. Biomedical Spectroscopy and Imaging, Volume 2/Issue 2. DOI: 10.3233/RNN-120303. Published by IOS Press.

Full text of the article is available to credentialed journalists upon request. Contact Esther Mateike, IOS Press, at +31 20 688 3355 or e.mateike@iospress.nl. Journalists wishing to interview the authors should contact Chelsea Whyte at 631-344-8671 or cwhyte@bnl.gov.

About Biomedical Spectroscopy and Imaging (BSI)

Biomedical Spectroscopy and Imaging is dedicated to providing a single forum for experts in spectroscopy and imaging as applied to biomedical problems, and also for life scientists who use these powerful methods for advancing their research work. BSI aims to promote communication, understanding and synergy across the diverse disciplines that rely on spectroscopy and imaging. It also encourages the submission of articles describing development of new devices and technologies, based on spectroscopy and imaging methods, for application in diverse areas including medicine, biomedical science, biomaterials science, environmental science, pharmaceutical science, proteomics, genomics, metabolomics, microbiology, biotechnology, genetic engineering, nanotechnology, etc. www.iospress.com/journal/biomedical-spectroscopy-and-imaging 

About IOS Press

Commencing its publishing activities in 1987, IOS Press serves the information needs of scientific and medical communities worldwide. IOS Press now (co-)publishes over 100 international journals and about 130 book titles each year on subjects ranging from computer sciences and mathematics to medicine and the natural sciences.

IOS Press continues its rapid growth, embracing new technologies for the timely dissemination of information. All journals are available electronically and an e-book platform was launched in 2005. 

Headquartered in Amsterdam with satellite offices in the USA, Germany, India and China, IOS Press has established several strategic co-publishing initiatives. Notable acquisitions included Delft University Press in 2005 and Millpress Science Publishers in 2008.

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