Copper May Trigger, Enhance Alzheimer's Disease

ROCHESTER, NYAlzheimer's disease has a new culprit, copper, according to a study appearing in the journal Proceedings of the National Academy of Sciences.

Copper seems to trigger the onset and enhance the progression of Alzheimer's by preventing the clearance and accelerating the accumulation of toxic proteins in the brain.

It is clear that, over time, coppers cumulative effect is to impair the systems by which amyloid beta is removed from the brain," said Rashid Deane, Ph.D., a research professor in the University of Rochester Medical Center (URMC) Department of Neurosurgery, member of the Center for Translational Neuromedicine, and the lead author of the study.  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 Alzheimers disease."

Copper is everywhere in the food industry, from drinking water, nutritional supplements and certain foods such as shellfish and nuts. The mineral plays an important role in bone growth, nerve conduction, the formation of connective tissue and hormone secretion, but it also, it can accumulate in the brain and cause blood brain barriers to break down resulting in toxic accumulation of the protein amyloid beta. In addition to copper, high blood sugar levels have been linked to increase risk of dementia as well.

Deane and colleagues used mice and human brain cells to conduct a series of experiments that show how copper accelerates the pathology of Alzheimer's.

Under normal circumstances, amyloid beta is removed from the brain by a protein called lipoprotein receptor-related protein 1 (LRP1). These proteinswhich line the capillaries that supply the brain with bloodbind with the amyloid beta found in the brain tissue and escort them into the blood vessels where they are removed from the brain.

Over a period of three months, the team dosed mice with copper. The exposure consisted of trace amounts of the metal in drinking water and was one-tenth of the water quality standards for copper established by the Environmental Protection Agency.

The levels were equivalent to what a typical person would consume in a regular diet.

The researchers found that the copper made its way into the blood system and accumulated in the vessels that feed blood to the brain, specifically in the cellular walls of the capillaries.

The researchers observed that the copper disrupted the function of LRP1 through a process called oxidation which, in turn, inhibited the removal of amyloid beta from the brain. They observed this phenomenon in both mouse and human brain cells.

The researchers then looked at the impact of copper exposure on mouse models of Alzheimers disease. In these mice, the cells that form the blood brain barrier have broken down and become leaky" a likely combination of aging and the cumulative effect of toxic assaults allowing elements such as copper to pass unimpeded into the brain tissue. 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 brains waste disposal system cannot clear.

This provides evidence that copper is a key player in Alzheimer's disease. Researchers also observed that copper provoked inflammation of brain tissue which may further promote the breakdown of the blood brain barrier and the accumulation of Alzheimers-related toxins. 

However, because metal is essential to so many other functions in the body, the researchers say that these results must be interpreted with caution.

Copper is an essential metal and it is clear that these effects are due to exposure over a long period of time," said Deane. The key will be striking the right balance between too little and too much copper consumption. Right now we cannot say what the right level will be, but diet may ultimately play an important role in regulating this process."