Word: amyloid
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Then, last year, the Amyloid People staged a surprise attack. First, researchers at Elan Pharmaceuticals of South San Francisco stunned their colleagues by reporting that they had taken mice genetically engineered to develop plaques and vaccinated them with a fragment of beta amyloid. Twelve months later, seven out of nine mice remained plaque free. Then the Elan team vaccinated year-old mice whose brains were riddled with plaques. Result: the plaques started to melt away. Elan quickly drew up plans to test the vaccine in humans...
That same year, other research teams, including one led by Selkoe, created yet another stir. They zeroed in on the elusive enzymes that snip the beta-amyloid fragment from the precursor protein. "We had the paper, and now we had the scissors," says Selkoe. If he is right, one of those scissors, gamma secretase, may actually be the presenilin-1 protein. Whatever the true identity of gamma secretase turns out to be, pharmaceutical companies are rushing to develop drugs that block it. Bristol-Myers Squibb has already started safety tests of one such compound and hopes to expand its study...
Many questions remain. For one thing, researchers are worried that gamma secretase may perform vital functions in the brain and that blocking it could cause serious side effects. Also, no one knows whether strategies aimed at lowering levels of beta amyloid will have any impact on the course of Alzheimer's disease--though if the beta-amyloid hypothesis is right, they should. Selkoe and other Amyloid People now see the disease process as a biochemical cascade; the event that triggers the cascade, they believe, is the accumulation of beta amyloid...
...essence, the brain perceives microscopic shards of beta amyloid as foreign bodies, and primitive immune cells called microglia that serve as biological garbage collectors valiantly and continuously try to clear them away. The result is a state of chronic inflammation that progressively injures nearby nerve cells. Among the powerful weapons the brain's immune system brings to bear are oxygen-free radicals, which is one reason many think that antioxidants like vitamin E may be helpful...
...wrong. He believes some still unidentified biochemical event precedes the formation of tangles and plaques, perhaps a malfunction in the machinery that puts proteins together. "The question from the therapeutic standpoint," he observes, "is, What's responsible for the symptoms of disease? What's killing the cells? Is it amyloid...