Word: amyloid
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Alzheimer's disease, many experts are all but convinced, starts with the abnormal buildup of a protein known as beta amyloid. The chief constituent of the scarlike plaques found in the brain of Alzheimer's patients, beta amyloid is made by nerve cells when beta and gamma secretase execute a one-two snip that cuts a larger precursor protein into a shorter fragment. Sometimes the fragment is 40 units long, sometimes 42. The slightly longer variant, scientists have found, is directly toxic to nerve cells. Among other things, it appears to stimulate the release of oxygen free radicals, thereby setting...
...known as presenilin 1 and presenilin 2. In a series of experiments, researchers established that these genes exercised tight control over the activity of gamma secretase. They found that the particular mutations in the Alzheimer's-prone families not only increased the rate at which gamma secretase produces beta amyloid but also enhanced its penchant for making the more toxic version...
...with a target. Inside nerve cells it competes with a third enzyme known as alpha secretase, whose activity, some think, may help protect the brain against Alzheimer's disease. When alpha makes the first cut in the precursor protein, gamma secretase makes a second cut that produces not beta amyloid but an innocuous protein fragment known as p3. Elan and Pharmacia, based in Peapack, N.J., among others, are actively working to develop beta secretase inhibitors...
...reasons to remain cautious. For one thing, it may turn out that both these secretases play vital roles in other aspects of cellular metabolism, so that interfering with them will come at the price of serious side effects. For another, it is still far from proven that beta amyloid is as central to Alzheimer's disease as, say, cholesterol is to heart disease. Says molecular neurologist Dr. Peter St. George-Hyslop of the University of Toronto: "We have a theory and experimental data that support that theory, but we won't know the theory is right until we have...
...number of researchers, for example, believe that elevated cholesterol may contribute not only to heart disease but to Alzheimer's disease as well. Researchers at New York University's Nathan Kline Institute put transgenic mice on high-fat diets, then observed an increase in the rate at which beta amyloid built up in their brains. When they gave the mice a drug that brought cholesterol down, the rate of accumulation slowed...