Word: amyloid
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Almost overnight, it seemed, scientific interest in the genetics of beta amyloid exploded. Researchers had long been aware that early-onset Alzheimer's, while rare, often ran in families. Could it be, they wondered, that the culprit was a mutant version of the APP gene? In 1991 scientists at London's St. 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...
...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...
What followed was a sustained scientific Donnybrook. Roses, whose penchant for plain speaking had long irritated his peers, was attacked--viciously, he says--and he proceeded to fight back in kind. He dubbed his opposition the Amyloid People and mercilessly taunted them. The plaques, he argued--and still argues--were just tombstones, markers of places where brain cells had died, not the cause of death. On one occasion, Roses sent Selkoe, who had co-founded a company to work on Alzheimer's therapeutics, a photograph inscribed with the message "Dennis, you're wrong--but you're going to be rich...
...grin. But he's now convinced that it's not the right gene. Tanzi, however, refuses to acknowledge defeat. "There's a ton of biology that suggests it's a good candidate," he says. Among other things, A2M appears to mediate the rate at which neurons produce beta amyloid...
...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...