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July 11th, 2012
06:27 PM ET
Rare genetic mutation protects against Alzheimer'sWith more than 5 million Americans suffering from Alzheimer's disease, the most common form of dementia, the race is on to surface clues about causes and prevention. An important breakthrough for the research field comes in the journal Nature this week. Researchers say they found a rare genetic mutation in Iceland that appears to protect against Alzheimer's disease. The mutation appears to slow the production of the beta-amyloid protein, long considered to be a cause of Alzheimer's. This mechanism helps validate the theory that beta-amyloid plaques - an accumulation of the protein - cause this form of dementia for which no cure has been found. The research team was led by Dr. Kari Stefansson, chief executive of the Icelandic company DeCode Genetics. They studied data from the genomes of nearly 1,800 Icelandic people. A genetic test for the protective mutation wouldn't make sense, since it's so rare, experts said. If you really wanted to know if you have it, your doctor probably couldn't tell you; it would require a specialized research lab, says Dr. Sam Gandy, director of the Mount Sinai Center for Cognitive Health. Mutations like this are "not so good for screening as they are for teaching what’s going on," said Rudolph Tanzi, a Harvard Medical School neurologist who was not involved in this study. Drugs attempting to clear some of those plaques out have so far failed to reverse the effects of dementia in clinical trials, but this new study drives home that targeting beta-amyloid is still correct, Tanzi said. There are going to be more failures before a successful treatment is found, Tanzi said. Drugs that have failed so far weren't getting into the brain, had harmful side effects or were just defective. A new wave of clinical trial results will come this fall - if they too fall short, this study reinforces that researchers should still go after beta-amyloid, Tanzi said. It might be another four or five years before drugs under development start showing more promising results, he said. "These are just not yet the right drugs, and I think the right ones are yet to come," he said. A successful protective drug against Alzheimer's would probably have to be taken for decades, like a statin to reduce risk of heart problems, said Dr. Robert Green, associate director of medicine in the division of genetics at Brigham and Women’s Hospital and Harvard Medical School. It could be something everyone takes, and perhaps the people most at risk of Alzheimer's would start on it earlier. This study suggests that when someone has this specific mutation, the amount of beta-amyloid protein released into his or her brain, which contributes to Alzheimer's, might be reduced by as much as 40%. This could explain lower rates of dementia. For most of us, who do not have this mutation, beta-amyloid protein gets released when the amyloid precursor protein (APP) on a brain cell is cut by two enzymes: Beta-secretase and gamma-secretase. (A third enzyme that snips it, alpha-secretase, actually prevents Alzheimer's-related plaques from forming). Drug developers have tried inhibiting gamma-secretase, but because that enzyme is responsible for so many other important things, these drugs were toxic. "You can't just hit it with a sledgehammer," Tanzi explains. The same goes for beta-secretase. "You need an enzyme that will block beta-secretase or gamma-secretase from clipping just APP, but you need to allow it to do its other jobs," Tanzi said. He and colleagues received a grant from the National Institute of Health to develop drugs along these lines. The Nature study suggests when people have the newly discovered mutation on the APP gene, they naturally experience less cutting from beta-secretase, resulting in lower amounts of beta-amyloid getting into the brain from birth. This seems to be a protection against Alzheimer's. In 1987, Tanzi led a group that discovered the APP gene, on which the protective mutation was found. This gene is associated with early-onset Alzheimer's disease. In 2009, his research team found two different rare mutations on this gene that raise the risk of Alzheimer's. Early symptoms of Alzheimer's include difficulty remembering names and recent events, apathy and depression. As the disease progresses, patients often exhibit disorientation, confusion and severe impairments in walking, speaking and swallowing. Lifestyle changes such as increased physical activity, lowered stress and healthy diet have found to be associated with staving off dementia, but there has been no definitive proof or treatment developed.
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Get a behind-the-scenes look at the latest stories from CNN Chief Medical Correspondent, Dr. Sanjay Gupta, Senior Medical Correspondent Elizabeth Cohen and the CNN Medical Unit producers. They'll share news and views on health and medical trends - info that will help you take better care of yourself and the people you love.
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