Word: beta-amyloid
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...Mary's Hospital Medical School screened the DNA of an Alzheimer's family and found what every geneticist in the field had been furiously looking for. The mutant APP gene sat on chromosome 21, and the single change in its DNA sequence occurred in the vicinity of the beta-amyloid fragment...
...Allen Roses, a rapier-tongued contrarian then at Duke University, challenged the beta-amyloid orthodoxy. He announced that he and his colleagues had found a major Alzheimer's-susceptibility gene that affected the late-onset forms of the disease. It was the gene for APOE4, a common variant of the APOE lipoprotein, which is one of the many workhorses of the body's cholesterol-transport system. What, everyone wondered, could this lipoprotein, a known risk factor for heart disease, possibly have to do with Alzheimer's? Very quickly, many concluded that Roses could not be right...
...1990s, the debate between the Baptists (the first three letters stand for beta-amyloid protein) and the Tauists had intensified--and for a while the Tauists appeared to be gaining ground. For one thing, the normal function of beta amyloid (if it had one) remained mysterious. All that scientists knew was that it was secreted by virtually every cell in the body, that it came primarily in two lengths, and that, in the brain, the slightly longer version was more likely to aggregate into plaques...
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...
...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...