UCLA scientists have created the first technique to image the earliest evidence of Alzheimer’s disease in the living brain — before the disorder begins attacking brain cells. Reported in the January issue of the American Journal of Geriatric Psychiatry, the technique will allow doctors to monitor the disease as it unfolds — speeding diagnosis, intervention and new therapies for the disorder that afflicts 10 percent of people older than 65.
UCLA researchers combined a new chemical marker called FDDNP with positron emission tomography (PET) to see for the first time the brain lesions indicative of Alzheimer’s disease in the living patient.
"We have developed the first tracer molecule that visually zeroes in on the brain lesions caused by Alzheimer’s disease," said principal investigator Dr. Jorge R. Barrio, UCLA professor of medical and molecular pharmacology.
"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 biobehavioral sciences.
Physicians regard these brain lesions, called amyloid plaques and tangles, as the definitive hallmarks of Alzheimer’s disease. Experts suspect that the lesions’ growth disrupts cell function and kills off brain cells, leading to disorientation and progressive memory loss.
Barrio and Small discovered that PET scans of patients injected with FDDNP showed the presence of early brain lesions — before the plaques are believed to destroy brain cells. If experts’ hypotheses about the lesions’ role prove accurate, UCLA’s technique could identify when medical intervention may still stave off 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," Barrio said. "So it’s the first place where scientists must seek evidence of the disease."
Before UCLA’s discovery, pathologists could make a definitive Alzheimer’s diagnosis only by brain autopsy. As a result, physicians were able to treat Alzheimer’s disease only after the disease has already caused apparent 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," Small said. "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," Barrio said. "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.
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’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. Co-authors 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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