Copper And Alzheimer's Disease: Researchers Finger Metal As Key Player In Neurodegenerative Condition

on August 19 2013 3:49 PM
coppertube
A copper tube. Wikimedia Commons/Maksim

A new study shows that long-term exposure to copper may be a key environmental factor in triggering the onset of Alzheimer’s disease, and could also possibly worsen the condition once it takes hold of a patient.

Copper can be found in a wide range of foods -- including shellfish, red meat, nuts and vegetables -- and can also make its way into drinking water that travels through copper pipes. While the body needs metals like copper to survive, scientists have also long suspected a copper imbalance plays some role in Alzheimer’s. For instance, in 2003, a pair of scientists from the Sun Health Research Institute in Arizona found that when rabbits were exposed to copper through their food and drinking water, there were higher accumulations of amyloid beta, a protein linked to Alzheimer’s, in the animals’ brains. But a team of British researchers recently argued in another paper published this past February that copper actually protects the brain by preventing beta amyloid from organizing into sheets that result in harmful plaques.

Now, researchers from the University of Rochester Medical Center have found a mechanism by which copper does seem to set the brain up for Alzheimer’s. Their results, published in the Proceedings of the National Academy of Science on Monday, suggest that the metal can accumulate in blood vessels and prevent the body from ferrying harmful amyloid beta proteins out of the brain. If copper crosses the blood-brain barrier, it also seems to stimulate the production of amyloid beta and encourage the protein to bind into larger complexes.

In their experiments, the scientists gave mice drinking water laced with relatively low levels of copper -- one-tenth of the maximum contaminant level recommended by the U.S. Environmental Protection Agency -- over a three-month period. They also examined the effects of copper directly on human and mouse brain cells.

Normally, the protein amyloid beta is taken out of the cell with the help of another protein called lipoprotein receptor-related protein 1, or LRP1. When copper builds up in the walls of blood vessels near the brain, it can bind to other molecules that interact directly with LRP1.

“What is happening is that the copper is damaging LRP1 by oxidation,” senior author Rashid Deane said in a phone interview. Once LRP1 gets damaged, it naturally starts to degrade.

Deane and his colleagues also found that in mice genetically engineered to simulate the effects of Alzheimer’s disease, copper crossed into the brain, thanks to flaws in the blood-brain barrier. The accumulated copper then stimulated activity in neurons that resulted in increased production of amyloid beta.

So, in some aged or genetically susceptible individuals, copper ingested from the environment could both undercut the body’s ability to get rid of amyloid beta as well as ramping up its production. It’s a one-two punch, says Deane, though there’s still a lot of work to be done. Their experiments only dealt with copper in drinking water, which is in a much more readily absorbed form; copper in digested food may not accumulate in the brain as easily. And Deane takes the view that Alzheimer’s is a multifactorial disease – there’s likely no one singular cause for the condition, but many interacting factors.

The finding does point a way towards possible treatments that could delay the onset of Alzheimer’s, or perhaps even arrest the condition’s course. Deane points to clinical trials (that he’s not involved in) which are testing out special molecules called “chelators,” which bind to copper and move it around.

“We may find a subpopulation [of Alzheimer’s patients] that could benefit from this therapy,” Deane says.

SOURCE: Singh et al. “Low levels of copper disrupt brain amyloid-beta homeostasis by altering its production and clearance.” Proceedings of the National Academy of Sciences published online 19 August 2013.

More News from IBT MEDIA