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Study confirms imaging compound identifies
amyloid-beta in human brain
Imaging with Pittsburgh Compound
B may track treatment results, not sufficient for diagnosis
BOSTON - March 12, 2007 - A team led by Massachusetts General
Hospital (MGH) investigators has confirmed that the imaging agent
Pittsburgh Compound B (PiB) binds to the protein in amyloid plaques
that characterize Alzheimer's disease in the human brain. Their
report in the March Archives of Neurology describes the first
postmortem neuropathological study of a dementia patient who had
previously participated in a PET imaging study using PiB.
"This report is an essential validation of the use of PET imaging
with PiB to identify amyloid-beta deposits in the brain and as a
marker of disease progression that could be used to track the benefit
of new treatments," says John Growdon, MD, director of the
MGH
Memory Disorders Unit, the paper's senior author. "It also
indicates that the interpretation of PiB PET scanning needs to be
done in the context of a patient's clinical symptoms and other diagnostic
studies."
Alzheimer's disease is characterized by plaques within the brain
of amyloid-beta protein, which is toxic to brain cells. Previous
studies have shown that PiB, invented by researchers at the University
of Pittsburgh School of Medicine, binds to amyloid-beta in the brains
of mice and can be detected by PET scan in the brains of human patients
with a diagnosis of probable Alzheimer's disease. But since a definitive
Alzheimer's diagnosis can be made only on autopsy, there had been
no confirmation that PiB in human brains was detecting amyloid-beta
deposits.
The Archives of Neurology report describes the case of an
elderly man with symptoms that could indicate several neurological
disorders. He was evaluated numerous times over a period of three
years, including a standard PET scan that produced results suggesting
Alzheimer's disease. His eventual diagnosis was dementia with Lewy
bodies, a condition that can exist along with Alzheimer's. He also
enrolled in a research study involving PiB imaging, and the results
of his scan showed the imaging compound had been taken up throughout
the cerebral cortex, the outer layer of the brain. Three months
after participating in the imaging study, the patient died at the
age of 76 following a head injury, and an autopsy was performed.
The autopsy confirmed the diagnosis of dementia with Lewy bodies
and had several findings characteristic of Alzheimer's disease.
While some plaques that typify Alzheimer's were seen, most amyloid-beta
was found in the walls of blood vessels, a condition known as cerebral
amyloid angiopathy.
"The distribution of amyloid seen at autopsy matched the overall
distribution seen in the PiB imaging study; levels were higher in
the cerebral cortex than in other areas of the brain," says
Matthew Frosch, MD, PhD, of the MassGeneral
Institute for Neurodegenerative Diseases (MGH-MIND), a study
co-author. "Features of Alzheimer's pathology, amyloid plaques
and neurofibrillary tangles, were observed, but not at a level that
would support a separate diagnosis of Alzheimer's disease."
The researchers note that, while their results confirm that uptake
of PiB indicates the presence of amyloid in the brain, a positive
PiB PET scan cannot be equated with a definitive Alzheimer's diagnosis.
"About 15 percent of control participants in previous PiB studies,
people with no cognitive impairment, had some level of PiB uptake,"
says Brian Bacskai, PhD, of MGH-MIND, the paper's lead author. "Some
participants who probably had Alzheimer's had low uptake, and uptake
levels varied for those with a diagnosis of mild cognitive impairment.
Once a safe and effective drug for removing amyloid from the brain
or preventing its accumulation is developed, it will be important
to see how closely PiB PET scans can track those effects."
Additional co-authors of the Archives of Neurology report
are Stefanie Freeman, MD, Scott Raymond, Jean Augustinack, PhD,
Keith Johnson, MD, Michael Irizarry, MD, and Bradley Hyman, MD,
PhD, of the MGH; William Klunk, MD, PhD, and Chester Mathis, PhD,
of University of Pittsburgh School of Medicine, the co-inventors
of PiB; and Steven DeKosky, MD, also of the University of Pittsburgh.
The study was supported by grants from the National Institutes of
Health, the Massachusetts Alzheimer's Disease Reseach Center, and
the MGH/Massachusetts Institute of Technology Udall Center of Excellence
in Parkinson's Disease Research.
Massachusetts General Hospital, established in 1811, is the original
and largest teaching hospital of Harvard Medical School. The MGH
conducts the largest hospital-based research program in the United
States, with an annual research budget of nearly $500 million and
major research centers in AIDS, cardiovascular research, cancer,
computational and integrative biology, cutaneous biology, human
genetics, medical imaging, neurodegenerative disorders, regenerative
medicine, transplantation biology and photomedicine. MGH and Brigham
and Women's Hospital are founding members of Partners HealthCare
HealthCare System, a Boston-based integrated health care delivery
system.
Media Contact: Sue
McGreevey, MGH Public Affairs
Physician Referral Service: 1-800-388-4644
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