Pittsburgh Compound B offers early proof of Alzheimer’s

Though University of Pittsburgh Alzheimer's disease researchers believed it all along, groundbreaking research now confirms that Pittsburgh Compound B binds to the beta-amyloid deposits found in the brains of patients with Alzheimer's. The finding is a major step toward an early, definitive diagnosis of the memory-stealing disease in living patients.

"As excited as researchers get, we are pretty excited," said senior author Dr. Steven T. DeKosky, a professor of neurology, psychiatry, neurobiology, and human genetics and director of the Alzheimer's Disease Research Center at the University of Pittsburgh.

Until now, the beta-amyloid deposits to which PIB binds have been confirmed only in the autopsied brains of Alzheimer's patients. The new findings correlate PIB-identified beta-amyloid deposits from living patients to their post-mortem autopsy results.

"It's very intriguing," DeKosky said. "We can't wait to see what happens."

He noted that scientists are presently using PIB as a marker in trials of anti-beta-amyloid drugs.

An estimated 4.5 million people in the U.S. have Alzheimer's disease, and that number is expected to triple over the next 50 years, according to a university press release. With such grim statistics, these latest findings will be of interest to every imaging specialist and clinician involved in the disease. They should be a hot topic at the June Society of Nuclear Medicine meeting in New Orleans.

Coupled with PET imaging, PIB can be injected into the bloodstream to enable researchers to visualize the brains of people suspected of Alzheimer's and see the location and distribution of the telltale beta-amyloid plaque deposits associated with the illness. These amyloid plaques, which are thought to kill brain cells, distinguish Alzheimer's from other dementia disorders.

PIB was invented and developed by Pitt researchers Chester Mathis, Ph.D., a professor of radiology and pharmaceutical sciences, and Dr. William Klunk, a professor of psychiatry and neurology. About 2000 people at 30 hospitals worldwide have been examined with the agent since 2003.

For this latest study, reported in the journal Brain, a 63-year-old woman with a clinical diagnosis of Alzheimer's underwent PIB-PET imaging. The scan showed significant retention of PIB in distinct regions of her brain. Upon her death 10 months later, her autopsied brain was analyzed using histological and biochemical assays to detect a variety of amyloid deposits, including beta-amyloid plaques.

The regions of her brain where the PET scans had identified the highest PIB levels before death correlated precisely with the regions of high beta-amyloid plaque concentration post-mortem.

To further validate the binding properties of PIB to beta-amyloid and the presence of Alzheimer's disease, sophisticated laboratory studies were performed on the autopsied brains of 27 other patients with confirmed Alzheimer's disease, according to the study report.

"In every subject, and with each test that we performed, our results supported the idea that PIB binds almost exclusively to beta-amyloid, which means that we can, with confidence, look to PIB to indicate the troublesome beta-amyloid deposits in brains of living patients," said lead author Dr. Milos Ikonomovic, an assistant professor of neurology and psychiatry at the University of Pittsburgh, in a statement.

The study was supported by grants from the National Institutes of Health, the Alzheimer's Association, the Department of Energy, and the Dana Foundation.

For more information from the Diagnostic Imaging archives:

Innovation drives growth of hybrid imaging

PIB-PET opens diagnostic front in Alzheimer's disease

Novel PET agent breaks through in Alzheimer's diagnosis

Autopsy confirms that compound binds to amyloid plaque in human brain