A New Clue To Alzheimer's

Few diseases exact such an awful toll as Alzheimer's. An estimated 4 million Americans are gradually losing mind and memory to the illness, yet no one knows its cause, let alone how to treat it. The search for clues has long centered on beta amyloid, a protein molecule that shows up in victims' brains, massed in hard clumps and surrounded by webs of dead neurons. Until last week, researchers assumed the amyloid protein was a product of the disease, not a normal substance. But three new studies have toppled that assumption, setting Alzheimer's research on a new course. The studies, appearing in the journals Science and Nature, reveal that beta amyloid pervades the body in a harmless, soluble form. That may seem a trifling insight. But if Alzheimer's involves the buildup of a naturally occurring chemical, then drugs that slow its production should help control the disease. Such drugs will take years to develop, but the new findings give scientists a set of long-awaited tools.

All three studies tackled the same basic question. To see if healthy people harbor the amyloid protein, teams based in Boston, Cleveland and San Francisco tested a range of cells and body fluids with newly developed molecular probes. To their surprise, they found the molecule everywhere they looked-in plasma, in spinal fluid, even in fetal neurons. No one knows what natural function the amyloid protein performs. Nor is it clear that the brain deposits associated with Alzheimer's disease result directly from a bodywide amyloid overload. When the Cleveland researchers tested 12 sufferers and 12 nonsufferers, they found "no obvious correlation between Alzheimer's disease and the amount of amyloid protein in cerebrospinal fluid." But even if Alzheimer's patients don't always exhibit high levels of circulating amyloid, says Dr. Dennis Selkoe, the leader of the Boston group, they must metabolize the molecule in unique ways-for it always collects in their brain tissue.

Now that they've identified the amyloid protein as a product of normal cells, scientists will be able to study its entire life cycle. And as their research pinpoints the chemical processes that can go awry, causing abnormal brain deposits, Alzheimer's should become easier to predict and diagnose. Indeed, a routine amyloid analysis may someday reveal as much about a person's health prospects as a cholesterol test does today. Early Alzheimer's detection would serve little purpose without advances in treatment, but last week's discovery should further that quest as well, by helping researchers isolate amyloid-blocking compounds. Scientists now know that normal cells will produce beta amyloid in a test tube. To test a potential inhibitor, one can simply add it to the same test tube and measure its effect. The San Francisco team has already started screening potential treatments that way. Compounds that show promise will be tested in animals and, eventually, people. Reliable treatments may still be a decade from fruition, but that's far closer than they were a week ago. "Until now," says Selkoe, "all we could do is scratch our heads."

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