Does Alzheimer’s confuse you? You’re not alone. In fact, one of the great mysteries of modern science is the question of what actually causes Alzheimer’s disease. For several years a group of Alzheimer’s disease researchers have believed that metals such as iron and copper play a role. Now a new study supports that theory.
Researchers at the University of Rochester Medical Center found that copper may trigger the onset of Alzheimer’s disease. Rashid Deane, Ph.D., lead author of the study, said that copper seems to prevent the brain from getting rid of a protein that forms the plaque that is the trigger of the disease.
“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 in a statement. The researchers, who published their work in Proceedings of the National Academy of Sciences showed that copper can cause the protective blood-brain barrier to break down — at least in mice.
Fascinating. But what we all really want to know is, should we try to reduce copper in our own diets? Copper is found in drinking water carried by copper pipes, nutritional supplements, red meats, nuts, shellfish, and even fruits and vegetables. It’s an important mineral in bone growth, nerve function and tissue formation. We need small amounts of it to function well, but exposure to high levels can cause Alzheimer’s-like symptoms. Will reducing the amount of copper we eat or drink reduce our chances of getting Alzheimer’s disease?
At a recent International Conference on Nutrition and the Brain, hosted by the Physician’s Committee for Responsible Medicine (PCRM), several of the speakers focused on metals in the brain — specifically copper and iron — and their possible role in Alzheimer’s disease.
Australian scientist Ashley Bush, M.D., director of the Oxidation Biology Laboratory at the Florey Institute of Neuroscience and Mental Health in Melbourne, Australia, was particu
A group of scientists directed by Dr. Rudolph Tanzi's team of the genetics and aging research unit at Massachusetts General Hospital and professor of neurology at Harvard Medical School
http://healthland.time.com/2013/04/26/alzheimers-advance-gene-could-help-to-clear-brain-plaques-responsible-for-the-disease reported in the journal Neuron earlier this year that they have pieced together the back story of one gene, known as CD33, that could lead to exciting new ways of removing the amyloid plaques that build up in the brains of Alzheimer’s patients and cause so many problems with memory and cognitive functions. When Dr. Tanzi’s team looked at the brains of patients who had died of Alzheimer’s, they found that CD33 also had a darker side. In patients with a higher burden of amyloid plaques, CD33 also appeared in excess. And so did tons of dead neurons. “At some point, as the amyloid is making the cells sick, and forming tangles as lots of neurons are dying, the microglia put on their battle gear and turn radical, killing whatever they think is attacking the brain,” says Tanzi. “The result is friendly fire, and they start to kill so many neurons that the microglia are now detrimental; they are no longer clearing but they’re rounding up nerve cells and shooting out free radicals and causing a lot of damage."...Instead of engulfing and removing the amyloid, microglia armed with CD33 were targeting healthy nerves instead. To confirm that, Tanzi’s team conducted a series of tests with cells in culture and in animals, and found that when microglia were stripped of CD33, they went back to performing their housekeeping duties as expected, sniffing out amyloid and pulling the protein out of circulation. Mice genetically engineered to develop Alzheimer’s plaques but without CD33 showed lower levels of amyloid plaques in their brains than animals with the gene, suggesting that the CD33 was clearing the protein away." This supports the genetic predisposition of the disease.
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"That clearance could be the key to alleviating some of the worst symptoms of the disease, experts say, since most people make amyloid protein but for some reason it starts to accumulate as we age. “What we discovered is that CD33 is a key switch so when the switch is off, and it is deactivated, there is more clearance of [amyloid,]” says Tanzi. “If we can now find drugs that inactivate CD33 it should allow more clearance of [amyloid] by the microglial cells.”
His group is already screening compounds to find those that might block CD33 from turning rogue, but the search will have to balance compounds that do a good job of keeping CD33 honest without compromising its ability to seek and destroy real invaders, as it was designed to do. “It’s something we have to keep an eye on for sure,” says Tanzi of the possibility that a CD33 blocker to treat Alzheimer’s could compromise immune functions and make patients more vulnerable to infections or other health issues.
But the discovery could be an important step toward finally developing an effective Alzheimer’s drug treatment, since clearing amyloid plaques could be critical in addressing the deposits of amyloid that mushroom throughout the brain as the disease progresses. “We just need to take advantage of the housekeeping functions of CD33 and entice them to stay helpful and not go crazy,” says Tanzi.
His research focuses on understanding how metals are binding with proteins connected with Alzheimer’s disease and whether using drugs to control copper and iron in the brain can help cure or prevent the disease. Bush and other researchers are currently testing one of those drugs on humans — in the fall we should know more about whether it works.
Based on the work of Bush and other scientists, the PCRM’s Dietary Guidelines for Alzheimer’s Prevention included the recommendation to “choose multivitamins without iron and copper and consume iron supplements only when directed by your physician.” This is controversial because even if these metals are some of the villians in Alzheimer’s, there’s no strong evidence that reducing them in your diet will help prevent the disease. Some scientists say copper may even be protective to the brain. But Deane cautiously suggests that people might take a take a closer look at the copper in their diets.
“Copper is essential. But maybe, just maybe, if we are finding that copper is creating a problem in the brain, we should back off on supplements, look at labels on foods and know how much copper we are putting in our bodies. We don’t need to overdo it,” he told CNN.
Unfortunately, like so many aspects of this scientific mystery, the jury is still out on this one. But I did take a close look at my 25-year-old rusty cookie sheet last night and wonder what might be leaking into my kids’ cookies and french fries. Might be time to invest in a new one.