New research suggests copper that enters the body at levels encountered in the average modern diet may be leading, eventually, to Alzheimer's disease - by reducing the body's ability to clear away toxic proteins in the brain, and also by encouraging the clumping of those proteins.

Copper is an essential trace element in the diet. With iron, it helps make red blood cells, and it is also essential for the health of the immune system, blood vessels, nerves, and bones.

Copper enters the body via many sources, including drinking water carried in copper pipes, and from foods such as shellfish, nuts, red meat and many fruits and vegetables, and also via food supplements.

But now a study that used cells from both mice and humans, led by Rashid Deane, a research professor in the University of Rochester Medical Center (URMC) in the US, shows that copper can also build up in the brain and disrupt the body's ability to clear away amyloid beta proteins before they form the plaques that are the hallmark Alzheimer's disease.

Prof Deane says:

"It is clear that, over time, copper's cumulative effect is to impair the systems by which amyloid beta is removed from the brain."

He and his co-authors, all with URMC, write about their findings in Monday's online issue of the Proceedings of the National Academy of Sciences.

Copper interfered with brain-protective cells

Normally, the body removes amyloid beta from the brain with the help of a protein called LRP1, short for lipoprotein receptor-related protein 1. This protein, which lines blood vessels in the brain, binds with amyloid beta and escorts it out of the brain.

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For their study, the team gave mice trace levels of copper for three months.

They found the metal collected in the cells walls of the fine vessels that feed blood to the brain.

The cells the copper collected in are an important part of the brain's defence mechanism, the so-called blood/brain barrier, which controls the substances that can pass in and out of brain tissue.

By collecting copper in their membranes, the cells were just doing their job.

But the researchers found that with time, through the process of oxidation, the copper build up in the cell walls started to affect the ability of LRP1 to escort amyloid beta proteins out of the brain. They saw this happen in both mouse and human brain cells.

Copper also stimulated plaque formation

In a further experiment, they then examined the process in live mice bred to develop Alzheimer's disease. They found the cells responsible for maintaining the blood/brain barrier could not cope: they became leaky, probably with age and repeated damage from toxins.

Had they not been leaky, the cells would have trapped the copper in their cell walls, but in the Alzheimer's mice, the blood-borne metal was able to pass unhindered through the blood/brain barrier.

As it met with brain tissue, the leaked copper stimulated brain cells to increase their production of amyloid beta.

The copper also had a direct effect on the toxic protein itself: it encouraged it to clump together and form the characteristic plaques of Alzheimer's disease.

Once amyloid beta forms these large clumps inside brain cells, the body's natural ways of eliminating it are overwhelmed and cannot cope: scientists believe this is how Alzheimer's starts and progresses.

In a final experiment, the team also found that copper led to inflammation of brain tissue, which may also speed up the breakdown of the blood/brain barrier and the subsequent build up of Alzheimer's toxins.

Levels of copper found in normal diet

The levels of copper the researchers used in their experiments were trace amounts, about one-tenth of that set by standards for water quality from the US Environmental Protection Agency.

Prof Deane says:

"These are very low levels of copper, equivalent to what people would consume in a normal diet."

But neither he nor his colleagues are suggesting people change their diets or intakes of copper on the basis of these findings, which they say should be interpreted with caution.

The body needs copper, it is an essential metal. The effects shown in this study are due to exposure over a long period, and the key is getting the balance between too much and too little.

"Right now we cannot say what the right level will be, but diet may ultimately play an important role in regulating this process," Prof. Deane says.

Help with finding for the study came from The Alzheimer's Association, the National Institute on Aging, and a pilot grant from the National Institute of Environmental Health Sciences.

This is not the first study to implicate copper in a neurodegenerative disease. In 2011, another group of US researchers reported how copper affected a protein associated with Parkinson's disease.

Written by Catharine Paddock PhD