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A Window on the Alzheimer’s Brain

A special dye called Pittsburgh compound B reveals damage on PET scans.

By Anita Slomski // Summer 2007
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Until recently the only way to know for sure whether a human brain was afflicted with the telltale plaques and tangles of Alzheimer’s disease was to dissect it after death. Although that’s useful, seeing what’s going on in the brain of a living patient would aid early diagnosis and make it easier to evaluate the effects of experimental and approved treatments.

In 1987, William E. Klunk, professor of psychiatry at the University of Pittsburgh, began searching for an agent that would stain amyloid plaques in living brain tissue so that abnormal deposits could be seen on positron emission tomography (PET) images. After hundreds of attempts, he finally found success with agents derived from a dye called Thioflavin T. Normally, the dye had a positive charge, but when the charge was eliminated, the compound was able to slip past the densely packed cells of the blood-brain barrier in Alzheimer’s mice and zero in on amyloid plaques. What’s more, it didn’t remain in the brain, where a foreign substance might cause problems, but was cleared within an hour.

In initial human tests performed on 25 people, the results were remarkable. Klunk received the brain scans via e-mail on Valentine’s Day 2002. “The images were clear and sharp, and we could see forests of plaques,” he says.

The improved version of the compound, now known as Pittsburgh Compound B (PiB), currently helps researchers learn how amyloid accumulates in the brain and how effective experimental drugs are in targeting amyloid deposits. But it could also work as a diagnostic tool, says Klunk. “Among people who score normally on cognitive tests, about one in five shows early evidence of amyloid deposits on scans done with PiB,” he says. Klunk envisions annual PET scans with PiB for people considered at high risk of developing Alzheimer’s, such as those with a strong family history of the disease. Once effective therapies have been developed, it might even make sense to screen everyone older than 60.

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