| UCLA scientists
have created the first technique to image the onset of Alzheimer's
disease in the living brain-before the disorder attacks brain
cells. The method will allow doctors to monitor the disease
as it unfolds, speeding diagnosis and new treatments, according
to a report in the January 2002 issue of the American Journal
of Geriatric Psychiatry. The technique will allow doctors to
monitor the disease as it progresses, speeding diagnosis, intervention,
and new therapies for the disorder that afflicts 10 percent
of people older than 65.
New tracking molecule
UCLA researchers combined a new chemical marker called FDDNP
with positron emission tomography (PET) to observe the brain
scarring, or "lesions," associated with Alzheimer's
disease in living patients. "This non-invasive method
will help us monitor new vaccines and drugs designed to prevent
and treat the brain damage caused by Alzheimer's disease,"
said co-author Dr. Gary Small, Parlow-Solomon Professor of
Aging and UCLA professor of psychiatry and bio-behavioral
sciences.
"This non-invasive method will help us monitor new vaccines
and drugs designed to prevent and treat the brain damage caused
by Alzheimer's disease," said Dr. Gary Small, Parlow-Solomon
Professor of Aging and UCLA professor of psychiatry and biobehavioral
sciences. Dr. Small co-authored the research report with Dr.
Jorge R. Barrio, UCLA professor of medical and molecular pharmacology.
Imaging plaques and tangles
Physicians regard these brain lesions, called amyloid plaques
and tangles, as the definitive hallmarks of Alzheimer's disease.
Experts suspect that the growth of the lesions disrupts cell
function and kills off brain cells, leading to disorientation
and progressive memory loss.
During the one-hour PET procedure, a technologist injects
the FDDNP tracer molecule into the patient's arm after the
patient enters the PET scanner. If lesions are present, the
physician will see an accumulation of FDDNP in the brain's
memory centers.
Barrio and Small discovered that PET scans of patients injected
with FDDNP showed the presence of early brain lesions-before
the appearance of plaques that are believed to destroy brain
cells. If the hypotheses about the role of the lesions in
Alzheimer's disease prove accurate, UCLA's technique could
identify when medical intervention might still be able to
delay or prevent the onset of disease.
Using PET, the UCLA team detected high concentrations of
FDDNP in the memory centers of nine Alzheimer's patients'
brains. To verify their findings, the researchers performed
a brain autopsy after one of the patients died. The post-mortem
tissue showed FDDNP-stained lesions in the brain's memory
centers, confirming the results of the patient's PET scan.
"When Alzheimer's disease strikes, the memory center
is the first location where plaques take root and destroy
brain cells," explained Barrio. "So it's the first
place where scientists must seek evidence of the disease."
Diagnosis after death
Before UCLA's discovery, pathologists could make a definitive
Alzheimer's diagnosis only by brain autopsy. As a result,
physicians could begin treatment only after the disease had
already caused noticeable damage to the patient's memory.
Furthermore, early clinical diagnostic methods produced accurate
results 55 percent of the time.
"Most forms of dementia clinically look the same,"
said Small. "But if we can pinpoint the specific form
of dementia, we can use the appropriate medication to postpone
onset of the disease. This is a major gain."
"Combining the FDDNP marker with PET scans will enable
us to better screen participants for clinical trials and produce
more accurate research results," added Barrio. "This
will bring new drugs to market faster with lower cost and
improved accuracy for patients."
Future directions
Pioneered by Dr. Michael Phelps, UCLA pharmacology chair,
PET scans can differentiate Alzheimer's disease from the normal
effects of aging. A drop in metabolism in one area of the
brain indicates decreased activity in that region.
Barrio and Small's next step will be to refine the FDDNP-PET
scan technique in order to monitor therapeutic drugs. The
research team is comparing the PET scans of a larger group
of Alzheimer's patients with those of unaffected individuals
and patients with other dementias.
Alzheimer's disease afflicts nearly 10 percent of people
older than 65. The condition often begins with mild memory
lapses, then gradually advances to dementia-a progressive
deterioration of memory, language and most mental functions.
Alzheimer's patients eventually become bedridden and require
constant care. The United States spends roughly $100 billion
on the disease per year.
The UCLA study was supported by grants from the U.S. Department
of Energy, Charles A. Dana Foundation, Alzheimer's Association,
and the Institute for the Study of Aging, Inc. Coauthors included
Kooresh Shoghi-Jadid, Eric Agdeppa, Vladimir Kepe, Linda Ercoli,
Prabha Siddarth, Stephen Read, Nagichettiar Satyamurthy, Andrej
Petric and Sung-Cheng Huang.
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