It would go too far to say that fishing the tributaries of Lake Erie led Chester Mathis and Dr. William Klunk to find a way to diagnose Alzheimer's disease. But hooking steelhead salmon did help keep them sane until they could finish their search.

	John Heller, Post-Gazette Dr. William Klunk, left, and Chester Mathis of the University of Pittsburgh, have received the MetLife Foundation Award for developing a dye that identifies amyloid plaques thought to cause Alzheimer's. Click photo for larger image.

"We have a rule," explained Mathis, senior chemist at the University of Pittsburgh positron emission tomography, or PET, facility. "We can talk about fishing at work, but we can't talk about work while fishing."

During the early years of Mathis' collaboration with psychiatrist Klunk, when laboratory dead-ends outnumbered advances, that rule was important. It has become less so in recent years, now that the duo appear to have found a way to use PET scans to visualize the brain plaques that are a hallmark of Alzheimer's.

In Washington, D.C., yesterday, Klunk and Mathis were honored for their discovery -- an imaging dye called Pittsburgh Compound B, or PIB -- as winners of the MetLife Foundation Award for Medical Research in Alzheimer's Disease. They will share the $700,000 award with two other winners -- Dr. John Morris of Washington University in St. Louis and Dr. Ronald Petersen of the Mayo Clinic.

Until PIB came along, the only way to diagnose Alzheimer's was to show that a patient's dementia wasn't the result of some other known cause. And even then, 10 to 15 percent of Alzheimer's diagnoses turn out to be wrong. The only way to definitively diagnose the disease has been to find amyloid plaques in the brain -- at autopsy.

But injecting PIB into patients allows the plaques to be seen using PET scans. This provides a means not only to diagnose the disease, but to monitor its progress and its response to drugs -- an important tool as researchers look for ways to slow or reverse the disease.

The lack of such a tool has caused much frustration. A few years ago, for instance, researchers testing a since-abandoned vaccine were encouraged that immunized people had no signs of amyloid plaques at autopsy, noted Klunk, director of psychiatry for the Alzheimer's Disease Research Center at Pitt. But they could never be sure -- did the vaccine cause the plaques to disappear, or were they never there because the patients were misdiagnosed?

When Klunk sought out Mathis six years ago at the suggestion of a psychiatry colleague, a solution to this problem was far from sure.

After a few months of working together, "he found out that I fish -- fly fish," Mathis recalled. "That took us to another level."

They began taking trips to Lake Erie together, where they fish strictly in streams. "I'll go in a boat," Mathis said, "when I can't walk anymore."

They josh each other about their respective skills. Klunk insists that Mathis catches more fish, while he often ends up with the biggest fish of the day. Mathis claims he doesn't keep count.

But they agree that fishing requires the same sort of persistence as medical research. "In fishing, you don't get a lot of strikes. You have to cast a lot to be successful," Mathis explained. Research also requires trying a lot of things that don't work to find the one thing that does.

PIB is one of those things that works.

Clinical trials of the imaging dye are under way at three sites in Europe and will soon begin at three U.S. sites, including Pittsburgh. A larger national trial of PIB is in the planning stages.

As the success of PIB has grown, so have the demands of the research lab. Both now devote most of their energies to the compound, as they do the lab work necessary to prove that PIB does everything it's supposed to do and to support the clinical studies.

"Success has really cut down on the time we have to fish," Mathis lamented.