Pittsburgh Compound-B Confirmed in Identifying
Alzheimer’s Brain Toxins
Significant step in enabling a definitive diagnosis
of Alzheimer’s in living patients
March 26, 2008 – A new study confirms that
Pittsburgh Compound-B (PiB) binds to the telltale beta-amyloid deposits
found in the brains of patients with Alzheimer’s disease. The finding by
University of Pittsburgh Alzheimer’s disease researchers 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 have been confirmed, without question, 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 Alzheimer’s, 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.
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It is estimated that up to 4.5 million people in
the United States have Alzheimer’s, including 50 percent of those older
than age 85 and 10 percent of those over age 65. The number of those
affected is expected to triple over the next 50 years.
The study is reported online in the journal
Brain.
Invented and 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
illness and see the location and distribution of the beta-amyloid plaque
deposits associated with Alzheimer’s.
The distinguishing factor between Alzheimer’s
disease 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 histological 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. See the PiB PET image scan on this page.
Beta-amyloid plaques, the hallmark of Alzheimer’s
disease, 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 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.
“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.
“This patient who selflessly and generously agreed
to PiB PET scanning and who gave us the gift of her brain has enabled us
to compare what we detected during her life to what we confirmed after
her death,” said Dr. Klunk.
“The findings from our study of her brain, coupled
with the further confirmation of the other 27 brains, tell us without a
doubt that PiB binds to beta-amyloid and that it is a reliable indicator
of the presence of Alzheimer’s disease in those who are suffering its
cruel effects.
“This work is an important step forward in the
development of new tools for both research and clinical care,” noted
Neil Buckholtz, Ph.D., chief of the Dementias of Aging Branch of the
National Institute on Aging, National Institutes of Health, which
supported the study.
“It provides additional evidence validating the use
of PiB to identify beta-amyloid deposits in living individuals and
advancing the potential use of PiB as an outcome measure in clinical
trials of anti-beta-amyloid therapeutics.”
Editor’s Notes:
For a free-access link to the PDF version of the
online article, please click
here.
In addition to Drs. DeKosky, Ikonomovic, Klunk and
Mathis, the research team included Eric Abrahamson, Ph.D., Julie Price,
Ph.D., Nicholas Tsopelas, M.D., Brian Lopresti, B.S., Scott Ziolko,
B.S., Wenzhu Bi, B.S., William Paljug, M.Sc., Manik Debnath, M.S.,
Caroline Hope, M.Sc., Barbara Isanski, M.Sc., and Ronald Hamilton, M.D.,
all of the University of Pittsburgh School of Medicine.
The study was supported by grants from the National
Institutes of Health, the Alzheimer’s Association, The U.S. Department
of Energy and the Dana Foundation.
