August 20, 2013
Copper Found To Play A Role In Onset, Progression Of Alzheimer’s Disease
redOrbit Staff & Wire Reports - Your Universe Online
An element that is essential to all living organisms could also be one of the primary environmental factors that can lead to the onset of Alzheimer’s disease, according to new research appearing in Monday’s edition of the journal Proceedings of the National Academy of Sciences.Copper, which is a key constituent of the respiratory enzyme complex cytochrome c oxidase, also appears to enhance the progression of the neurodegenerative condition, lead author Rashid Deane of the University of Rochester Medical Center (URMC) Department of Neurosurgery and his colleagues have discovered.
It does this by preventing the brain from clearing out toxic proteins, causing them to accumulate. When copper builds up in the brain, it can cause the blood brain barrier (which controls what enters and exists the brain) to break down. That causes amyloid beta, a toxic protein produced as a by-product of cellular activity, to accumulate.
“It is clear that, over time, copper's cumulative effect is to impair the systems by which amyloid beta is removed from the brain,” Deane, who is also a member of the Center for Translational Neuromedicine (CTN) explained in a statement. “This impairment is one of the key factors that cause the protein to accumulate in the brain and form the plaques that are the hallmark of Alzheimer's disease.”
Exposure to copper is all but avoidable, the researchers point out. In addition to being found in foods such as red meats, shellfish, nuts and many different types of fruits and vegetables, it can also be found in drinking water carried by copper pipes and nutritional supplements. The body uses it in nerve conduction, bone growth, connective tissue formation and hormone secretion, Deane’s team noted.
The researchers conducted a series of experiments using both mouse and human brain cells, and through their research they were able to locate the molecular mechanisms through which copper accelerates the pathology of Alzheimer's disease. Typically, amyloid beta is cleared out of the brain through a protein known as lipoprotein receptor-related protein 1 (LRP1).
Those proteins bind with the amyloid beta found in the brain tissue and lead them into the blood vessels, where they are removed from the brain. During their experiments, however, the research team exposed otherwise normal mice to copper over a period of three months. They placed trace amounts of the metal in their drinking water, creating a concoction that was one-tenth of EPA-approved water quality standards for copper.
"These are very low levels of copper, equivalent to what people would consume in a normal diet." said Deane. Even so, he and his associates found the copper found its way into the rodents’ circulatory system and accumulated in the blood vessels (specifically, the cellular capillary walls) that carry blood into the brain.
These cells are an essential part of the brain’s defense system, and in this instance the capillaries help keep the copper from entering the brain. Over time, however, the metal can accumulate. Deane’s team observed the element disrupted the function of LRP1 through the process of oxidation, which ultimately resulted in amyloid beta from being removed. The phenomenon was reportedly detected in both mouse and human brain cells.
The study authors then looked at the impact of copper exposure on mouse models of Alzheimer’s disease. They discovered the blood brain barrier cells in those mice had broken down and become “leaky,” which they attribute to a combination of aging and the cumulative impact of copper being allowed to pass through to the brain.
“They observed that the copper stimulated activity in neurons that increased the production of amyloid beta. The copper also interacted with amyloid beta in a manner that caused the proteins to bind together in larger complexes creating logjams of the protein that the brain's waste disposal system cannot clear,” URMC explained.
“This one-two punch, inhibiting the clearance and stimulating the production of amyloid beta, provides strong evidence that copper is a key player in Alzheimer's disease,” he added. “In addition, the researchers observed that copper provoked inflammation of brain tissue which may further promote the breakdown of the blood brain barrier and the accumulation of Alzheimer's-related toxins.”
Deane advises approaching the study results with caution, since copper is essential to numerous biological functions. He says it will be important for people to make sure they consume enough of the mineral without being exposed to too much of it. While he said his team cannot say for sure what the correct level is, but that diet would likely play a key role in the regulation of this process.