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."
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.
Note: This story has been adapted from a press release originally issued by UCLA and posted on the Web at www.newswise.com. Any opinions expressed in this press release are those of the UCLA and not Rutgers University or Memory Loss and the Brain.
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