Imaging Agent Identifies Alzheimer's Disease Brain Toxins

The finding is a significant step toward enabling clinicians to provide a definitive diagnosis of Alzheimer's disease in living patients.

Until now, the beta-amyloid deposits to which PiB binds were confirmed only in the autopsied brains of patients afflicted with Alzheimer's. The new findings, which correlate PiB-identified beta-amyloid deposits from living patients to their post-mortem autopsy results, will ultimately aid in the early diagnosis of AD, help clinicians monitor the progression of the disease, and further the development of potential treatments.

"This is final confirmation of what we have believed all along--that Pittsburgh compound-B allows us to accurately assess the amount of beta-amyloid plaques in brains of people afflicted with Alzheimer's,” said senior author Steven DeKosky, M.D., professor of neurology, psychiatry, neurobiology, and human genetics and director of the Alzheimer's Disease Research Center at the University of Pittsburgh (Pitt; PA, USA).

Developed by Pitt researchers Chester Mathis, Ph.D., professor of radiology and pharmaceutical sciences, and William Klunk, M.D., Ph.D., professor of psychiatry and neurology, PiB is a radioactive compound that, when coupled with positron emission tomography (PET) imaging, can be injected into the bloodstream to enable researchers to visualize the brains of people with the memory-stealing disorder and visualize the location and distribution of the beta-amyloid plaque deposits associated with AD. The distinguishing factor between AD and other dementias is the presence of these amyloid plaques, which are thought to kill brain cells.

In the study, a 63-year-old woman with a clinical diagnosis of Alzheimer's underwent PiB PET imaging. The PET scan showed significant retention of PiB in distinct regions of her brain. Upon her death 10 months later, her autopsied brain was analyzed using histologic and biochemical assays to detect a variety of amyloid deposits, including the 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 concentrations in her autopsied brain.

Beta-amyloid plaques, the hallmark of AD, are just one type of amyloid structure that can be found in diseased brains. However, other forms of amyloid are not thought to be specific for Alzheimer's, or they have significantly different roles in the pathogenesis of this disease. To additionally 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 AD disease.

"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 the lead author Milos Ikonomovic, M.D., assistant professor of neurology and psychiatry at the University of Pittsburgh.

The study was published in the Advance Access online edition of the journal Brain on March 12, 2008.


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