Exposure to copper may trigger Alzheimer's by accelerating plaque buildup in the brain which leads to the neurodegenerative disease, a new study claims.
Copper appears to be one of the main environmental factors that trigger the onset and enhance the progression of Alzheimer's disease by preventing the clearance and accelerating the accumulation of toxic proteins in the brain, researchers from University of Rochester Medical Center said.
"It is clear that, over time, copper's cumulative effect is to impair the systems by which amyloid beta is removed from the brain," said Rashid Deane, 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 Alzheimer's disease," said Deane.
Copper's presence in the food supply is ubiquitous. It is found in drinking water carried by copper pipes, nutritional supplements, and in certain foods such as red meats, shellfish, nuts, and many fruits and vegetables.
However, the study shows that copper can also accumulate in the brain and cause the blood brain barrier - the system that controls what enters and exits the brain - to break down, resulting in the toxic accumulation of the protein amyloid beta, a by-product of cellular activity.
Using both mice and human brain cells Deane and his colleagues conducted a series of experiments that have pinpointed the molecular mechanisms by which copper accelerates the pathology of Alzheimer's disease.
Under normal circumstances, amyloid beta is removed from the brain by a protein called lipoprotein receptor-related protein 1 (LRP1). These proteins - which line the capillaries that supply the brain with blood - bind with the amyloid beta found in the brain tissue and escort them into the blood vessels where they are removed from the brain.
The research team "dosed" normal mice with copper over a three month period.
"These are very low levels of copper, equivalent to what people would consume in a normal diet," said Deane.
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.
These cells are a critical part of the brain's defence system and help regulate the passage of molecules to and from brain tissue. In this instance, the capillary cells prevent the copper from entering the brain. However, over time the metal can accumulate in these cells with toxic effect.
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 study appears in the journal Proceedings of the National Academy of Sciences.
