Test May Detect Alzheimer's Sooner

A new test that can detect the presence of plaques in the brain, evidence of Alzheimer's disease, could offer the hope of early diagnosis and perhaps better treatment if it works as well in people as in animals.

A chemical called PIB was able to cross the blood-brain barrier and bind to the amyloid plaques in the brains of mice with Alzheimer's, which allowed researchers to diagnose the disease by detecting the chemical.

The chemical quickly cleared out of the brains of mice without the disease, according to a team of researchers led by Dr. Brian J. Bacskai at Massachusetts General Hospital.

The next step, already under way in Pittsburgh and in Uppsala, Sweden, is to test the chemical in people.

Currently, Alzheimer's sometimes is indicated by symptoms, but a definite diagnosis can be made only after death.

While medicine has no current therapy for Alzheimer's, approaches from drugs to a vaccine are being studied.

The ability to diagnose the disease in its early stages would be important, because it would allow any new therapy to be started before much damage had been done, said Dr. William E. Klunk, a member of Bacskai's group, who is leading the human study at the University of Pittsburgh School of Medicine. Their findings are being published in this week's online issue of Proceedings of the National Academy of Science.

"All the evidence points to the fact that (Alzheimer's) pathology starts a decade or more before symptoms appear," said Klunk, so having a good way to detect plaques could get treatment started early.

The mouse studies confirmed that PIB binds directly to the amyloid plaques associated with Alzheimer's. Researchers studied the tissue through a hole in the skulls of the mice, using a multiphoton microscope that shows such minute tissues.

PET scans used on humans lack such fine resolution, but Klunk said they can detect the presence of PIB in areas of the brain, and knowing that the chemical binds to the plaques will inform that the problem is developing.

"It's like looking down from 30,000 feet and seeing a forest, but you can't tell what kind of trees are there," he said. Bacskai's "technique takes us to ground level."

Bacskai said PIB has been studied for toxicology and found to have no side effects. When injected in the tails of mice it moved quickly to the brain and bound to the plaques, remaining detectable for up to three days in some cases. When the mouse brains were dissected later, researchers were able to determine that PIB - Pittsburgh compound B - does not bind to white matter in the brain.

The finding was welcomed by Dr. F. Reed Murtagh, director of neuroradiology at the University of South Florida, who has also studied ways of detecting Alzheimer's.

Murtagh, who was not part of Bacskai's team, called the development terrific because it could lead to diagnosis in people.

"Nobody can diagnose definite AD - yet. This new stuff might allow us to do that," he said.

By Randolph E. Schmid