New research finds that copper in amounts readily found in our drinking water, the foods we eat and the vitamin supplements we take likely plays a key role in initiating and fueling the abnormal protein build-up and brain inflammation that are hallmarks of Alzheimer's disease.
While the mineral is important to healthy nerve conduction, hormone secretion and the growth of bones and connective tissue, a team of researchers from the University of Rochester Medical Center suggested that too much of it may be a bad thing, and they set about to explore copper's dark side.
What they found, said neuroscientist Rashid Deane, is "pretty scary": A steady diet of copper, even at entirely allowable levels, breaks down the barrier that keeps unwanted toxins from entering the brain, and that it fuels an increase in production of beta-amyloid but impedes the performance of proteins that clear the stuff from the brain.
On top of that, Deane's team found that copper accumulation in the brain causes inflammation in brain tissues. At low levels and for short durations, that may be a good sign that brain tissues are responding to the danger of excess beta-amyloid proteins and are trying to expel them, Deane said. In time, however, neuro-inflammation can overwhelm the brain and begin to damage cells, he added.
Copper is found in a wide range of the foods we eat, including red meat, shellfish, nuts and many fruits and vegetables, as well as in many vitamin supplements. It also leaches from copper pipes into the water we drink. While we take in copper from foods, it is most readily absorbed into the bloodstream in its "free" form, say researchers -- when it is suspended in water.
The research, which lay out the case against a long-suspected culprit in Alzheimer's disease, is published Monday in the journal PNAS.
Deane said that, in the absence of effective treatments for Alzheimer's disease, his team's findings suggest a way to prevent the memory-robbing disorder or slow it once it has taken hold. One drug candidate currently in Phase 2 trials -- an agent that binds with copper molecules and escorts them out of the body -- might well do that, said the study's lead author. But even now, Deane said, consumers could be checking their vitamin supplements for copper and researching whether their water filters are equipped to remove copper from their drinking supply.
"The key will be striking the right balance between too much and too little copper consumption," Deane said. "Right now, we cannot say what the right level will be. But diet may one day play an important role in regulating this process."
Deane's team worked with mice and with human brain cells that play a key role in forming the blood-brain barrier to detect the mechanisms by which copper might start, drive or worsen Alzheimer's disease. They noted that in the elderly, the blood-brain barrier becomes "leaky," letting in larger toxic molecules circulating the blood. So too does the concentration of copper in the brain's small blood vessels increase with age.
Starting in the mouse-equivalent of young adulthood, they fed mice a regular diet, but gave half of them water that contained levels of copper equal to one-tenth the maximum allowed by the Environmental Protection Agency. The other half were given double-distilled water with a very low copper content -- less than 2% of that given to the high-copper group. In a second experiment, older mice bred for their propensity to develop beta-amyloid plaques were fed the copper-tainted water or the low-copper water.
After three months, the effects were dramatic: In the mice who took in high doses of copper, the scientists observed that copper accumulated in the small blood vessels of the brain. Compared to mice on low doses of copper, the high-copper mice showed four times fewer levels of a protein called LRP1, which transports beta-amyloid and other debris out of the brain. They also showed abnormally high levels of beta-amyloid production and of neuro-inflammation.