Science + Technology

UCLA Researchers Invent First Technique to Image Alzheimer's Onset; Findings Will Speed Diagnosis, Intervention and New Therapies

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UCLA scientists havecreated the first technique to image the earliest evidence of Alzheimer'sdisease in the living brain — before the disorder begins attacking braincells. Reported in the January issue ofthe American Journal of Geriatric Psychiatry, the technique will allow doctorsto monitor the disease as it unfolds — speeding diagnosis, intervention and newtherapies for the disorder that afflicts 10 percentof people older than 65.

UCLA researcherscombined a new chemical marker called FDDNP with positron emission tomography(PET) to see for the first time the brain lesions indicative of Alzheimer'sdisease in the living patient.

"We havedeveloped the first tracer molecule that visually zeroes in on the brainlesions caused by Alzheimer's disease," said principal investigator Dr. JorgeR. Barrio, UCLA professor of medical and molecular pharmacology.

"This non-invasivemethod will help us monitor new vaccines and drugs designed to prevent andtreat the brain damage caused by Alzheimer's disease," saidco-author Dr. Gary Small, Parlow-Solomon Professor of Aging and UCLAprofessor of psychiatry and biobehavioral sciences.

Physicians regardthese brain lesions, called amyloid plaques and tangles, as the definitivehallmarks of Alzheimer's disease. Experts suspect that the lesions' growthdisrupts cell function and kills off brain cells, leading to disorientation andprogressive memory loss.

Barrio and Small discovered that PET scans of patients injectedwith FDDNP showed the presence of early brain lesions — before the plaques arebelieved to destroy brain cells. If experts' hypotheses about the lesions' roleprove accurate, UCLA's technique could identify when medical intervention maystill stave off or prevent the onset of disease.

Using PET, the UCLA team detected high concentrations of FDDNP inthe memory centers of nine Alzheimer's patients' brains. To verify theirfindings, the researchers performed a brain autopsy after one of the patientsdied. The post-mortem tissue showed FDDNP-stained lesions in the brain's memorycenters — confirming the results of the patient's PETscan.

"When Alzheimer's disease strikes, the memory center is the firstlocation where plaques take root and destroy brain cells," Barrio said. "Soit's the first place where scientists must seek evidence of the disease."

Before UCLA's discovery, pathologists could make a definitiveAlzheimer's diagnosis only by brain autopsy. As a result, physicians were ableto treat Alzheimer's disease only after the disease has already caused apparentdamage to the patient's memory. Furthermore, early clinical diagnostic methodsproduced accurate results 55 percent of the time.

"Mostforms of dementia clinically look the same," Small said. "But if we canpinpoint the specific form of dementia, we can use the appropriate medicationto postpone onset of the disease. This is a major gain."

"Combining the FDDNP marker with PET scanswill enable us to better screen participants for clinical trials and producemore accurate research results," Barrio said. "This will bring new drugs tomarket faster with lower cost and improved accuracy for patients."

Pioneered by Dr. Michael Phelps, UCLA pharmacology chair, PET scanscan differentiate Alzheimer's disease from the normal effects of aging. A dropin metabolism in one area of the brain indicates decreased activity in thatregion.

During the one-hour PET procedure, a technologistinjects the FDDNP tracer molecule into the patient's arm after the patiententers the PET scanner. If lesions are present, the physician will see anaccumulation of FDDNP in the brain's memory centers.

Barrio and Small's next step will be to refine the FDDNP-PET scantechnique in order to monitor therapeutic drugs. The research team is comparingthe PET scans of a larger group of Alzheimer's patients with those ofunaffected individuals and patients with other dementias.

Alzheimer's disease afflicts nearly 10 percent of people older than65. The condition often begins with mild memory lapses, then gradually advancesto dementia — a progressive deterioration of memory, language and most mentalfunctions. Alzheimer's patientseventually become bedridden and require constant care. The United States spends roughly $100billion on the disease per year.

The UCLA study was supported by grants fromthe U.S. Department of Energy, Charles A. Dana Foundation, Alzheimer'sAssociation, and the Institute for the Study of Aging Inc. Co-authors includedKooresh Shoghi-Jadid, Eric Agdeppa, Vladimir Kepe, Linda Ercoli, PrabhaSiddarth, Stephen Read, Nagichettiar Satyamurthy, Andrej Petric and Sung-ChengHuang.

-UCLA-

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