'Bio-Barcode' Alzheimer's Test Only a 1st Step

Experts impressed with researchers' efforts but say larger, more comprehensive studies needed

TUESDAY, Feb. 1, 2005 (HealthDay News) -- A dose of reality has been administered to a new test that may be able to diagnose Alzheimer's disease while the person is still alive.

The study was small, but the results were dramatic, and that has led medical experts to predict that a test for people who are living isn't that far away. But other experts are quick to point out that much larger and more comprehensive research is needed to bring such a test to reality.

Scientists reported in this week's Proceedings of the National Academy of Sciences that they had successfully used a sensitive new "bio-barcode" test to detect proteins related to Alzheimer's disease in spinal fluid. The study, however, involved only 30 people, and only half of them had Alzheimer's.

"The technique has potential for being very sensitive and important, but it's still quite new and underutilized," said Mony de Leon, director of the Center for Brain Health and a professor of psychiatry at New York University School of Medicine.

"If it holds up with a large number of people, I think that's going to be very, very helpful in terms of finding ways of predicting and diagnosing the disease," said Dr. Sam Gandy, vice president of the Alzheimer's Association's Medical and Scientific Advisory Council and director of the Farber Institute for Neurosciences at Thomas Jefferson University in Philadelphia. "Even better, if they can correlate it with the disease, it would be useful for measuring the effectiveness of anti-amyloid drugs."

The issue of diagnosing Alzheimer's disease, the most common neurodegenerative dementia, takes considerable priority among physicians. About 4 million Americans are afflicted with the disease, which progressively robs them of their memory and cognitive abilities. A growing number of people will develop the disease as the population ages, medical experts predict.

Currently, the only sure way to tell if a person had Alzheimer's is through an autopsy. While the person is living, however, the most perceptive way to tell is through neuropsychological testing.

"In the hands of a trained expert, this can really have accuracy in the 90s [percent]," Gandy said.

But diagnosing Alzheimer's can be an arduous process involving blood tests, spinal taps and imaging to rule out other causes. Most generalists are not comfortable making the diagnosis, Gandy added.

Because Alzheimer's involves the buildup of abnormal proteins in the brain, much effort has been focused on finding remnants of those proteins in other areas of the body, a task that has proved difficult.

"The material that we want to look at is in between the nerve cells inside the brain," Gandy pointed out. Because of the blood-brain barrier, it's unlikely that a blood test holds the key.

The researchers from Northwestern University decided to try a "bio-barcode" test, which has been used to detect a marker for prostate cancer. The test, which is more than 100,000 times as sensitive as conventional methods, looks for proteins and nucleic acids, and they don't always have to be inside the brain to be detected. The reason it's called a bio-barcode is because many of the substances in the strands of DNA are magnetic and can "read" the same way a consumer bar code can.

This time, they used it to detect a brain protein called amyloid-beta-derived diffusable ligand (ADDL) in spinal fluid.

They obtained samples of spinal fluid from 30 people, half of whom had Alzheimer's. The Alzheimer's group had higher levels of ADDL and the concentration of the protein tended to increase with more severe disease.

In addition, there was little overlap between the two groups. "The separation between controls and Alzheimer's patients was impressive, and if that holds up with a large number of people, I think that's going to be very, very helpful," Gandy said.

What would be even better, he added, is if levels of ADDL correlated with how far the disease has progressed. This would give scientists a way to measure the effectiveness of new therapies.

"Having an endpoint for these drugs would really accelerate drug discovery," Gandy said. "A lot of CEOs are afraid to greenlight [approve] clinical trials because they have a drug to target amyloid but absolutely zero in terms of measuring."

Another promising diagnostic tool that is in development is amyloid imaging, but the ADDL test would be more convenient and less expensive, Gandy said. It's not quite as convenient as a blood test because it involves a spinal tap, but a blood test for Alzheimer's is unlikely.

The barcode test is also biologically plausible. "It makes biological sense. That gives it some increased credence," Gandy said.

For now, anyway, diagnosis of this devastating disease is probably going to involve a number of different tests. "It looks to me that where we're ending up, at least for the short term, is an array of different diagnostic tests," de Leon said. "Any one test alone wouldn't give you the full story, but the combination would give you incontrovertible evidence."

More information

Visit the Alzheimer's Association for more on diagnosing the disease.

SOURCES: Mony de Leon, Ed.D., director, Center for Brain Health, and professor, psychiatry, New York University School of Medicine, New York City; Sam Gandy, M.D., Ph.D., vice president, Medical and Scientific Advisory Council, Alzheimer's Association, and director, Farber Institute for Neurosciences, Thomas Jefferson University, Philadelphia; Jan. 31-Feb. 4, 2005, Proceedings of the National Academy of Sciences
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