EmailEmail
PrintPrint
'Pittsburgh' compound helps track Alzheimer's
Thursday, January 22, 2004

A protein that clings to the brain plaques of Alzheimer's disease victims could help doctors definitively diagnose the disease, as well as lead to improved understanding of what causes the disease and how it progresses.

By allowing researchers to follow the progression of the disease in living patients, the substance -- a dye called Pittsburgh Compound B, or PIB -- might also be useful in monitoring the effects of powerful drug treatments.

In a study published yesterday in an early online edition of the Annals of Neurology, researchers from the University of Pittsburgh and Sweden's Uppsala University reported injecting trace amounts of the dye into Alzheimer's patients and healthy counterparts. The dye can be imaged in the brain using a technique called positron emission tomography, or PET.

The compound's co-developer, Chester A. Mathis of the Pitt medical school, said the PET scans showed about twice as much of the compound, which attached to the amyloid plaques that are characteristic of Alzheimer's, accumulated in patients with dementia than in those without.

"If we're going to be able to attack the primary pathology of the disease, we need to be able to see it," said Dr. Steven DeKosky, director of the Alzheimer's Disease Research Center at Pitt "And this is a way for us to see it."

The disease is usually diagnosed after death because that's the only time the brain can be examined for the hallmark plaques.

For the study, PET scans with the compound were conducted in 16 people clinically diagnosed with mild Alzheimer's disease, six healthy elderly people and three 21-year-old college students.

Overall, the dementia patients had about twice as much of the compound in areas of the brain known to accumulate amyloid.

The Alzheimer's Association, which helped fund the work, lauded the findings, but cautioned that the trial was small.

"Many more patients need to be studied to confirm and extend these findings," a statement from the association said. "However, the potential repercussions are very wide-ranging."

The researchers noted that three of the patient participants were at the lowest end of the range, bordering normal values. That raised a question.

"One explanation is that PIB is not sensitive to mild Alzheimer's disease, but the other explanation is they're not AD [Alzheimer's disease] subjects at all," Mathis explained.

He said a review of the three patients' cases showed that while they had some cognitive changes suggesting dementia, they had not worsened in the subsequent five years and two of them had improved over time, which is not typical of Alzheimer's.

Another curious finding was that the oldest of the elderly, healthy participants appeared to have amyloid values that approached those seen in the patients.

Upon further testing, "there were some cognitive deficits there," Mathis said. "It looked like he might have perhaps mild AD or presymptomatic disease."

The study participants will be followed regularly to see what happens, he added.

The Pittsburgh compound could allow doctors to identify the presence of amyloid and thus make a definitive diagnosis while the patient is still alive.

But the primary goal was to give researchers a way of tracking the amount of amyloid and the impact of plaque-targeting drugs, which DeKosky called "our big hopes for the future."

For example, Mathis said, "you want to be able to see that there's some [amyloid] now and there's less in a year, and it's all gone in two years" after treatment.

The technique could also answer other basic questions: When does amyloid deposition start? How much is present before symptoms appear? Does it continue to accumulate or does it level off eventually?

DeKosky has joined the researchers to develop studies that look at those issues, as well as amyloid deposition at different stages of the disease, during normal aging and in people who have familial Alzheimer's disease.

"This is the first and best compound that actually lets us see this inside the human brain in a fashion that isn't harmful and could be repeated," DeKosky said.

First published on January 22, 2004 at 12:00 am
Anita Srikameswaran can be reached at anitas@post-gazette.com or 412-263-3858.
Featured Homes