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Another Blood Test for Alzheimer's Shows Promise

By Jenifer Goodwin
HealthDay Reporter

WEDNESDAY, Aug. 3 (HealthDay News) -- A blood test that screens for certain markers in the blood called "autoantibodies" is showing promise in diagnosing Alzheimer's disease, researchers report.

The blood test correctly detected Alzheimer's disease in people already diagnosed with the devastating brain disorder with 96 percent accuracy, according to the researchers. The test could also distinguish who didn't have the disease from a control group of non-affected adults with 92.5 percent accuracy.

Though outside experts said the findings may be another step toward a quicker, easier way to diagnose Alzheimer's, they cautioned that there's still a long way to go.

The researchers who developed the test have not yet determined how early in the course of the disease the test works, such as whether the test would be able to detect people with the earliest signs of the disease or even before symptoms appeared, said Dr. Aron Buchman, a neurologist in the Rush Alzheimer's Disease Center at Rush University Medical Center in Chicago who was not involved with the research. He pointed out that the patients tested had already been diagnosed with Alzheimer's.

"This is important work that is at the edge of the envelope where the field is moving," said Buchman. "But Alzheimer's disease is a progressive disorder that takes many years to develop, with the end stage being dementia. This study didn't look at any people with mild cognitive impairment [mild memory loss that may progress to dementia] or who had Alzheimer's pathology in the brain but were not yet having clinical symptoms."

The study is published in the Aug. 3 online edition of PLoS ONE.

In the study, researchers at the University of Medicine and Dentistry of New Jersey-School of Osteopathic Medicine put a drop of blood taken from 50 people with Alzheimer's disease and 40 people without dementia onto slides called "human protein microarrays." The slides contained more than 9,400 human protein antigens, about one-third of all proteins made by humans.

Antigens stimulate the production of antibodies, and the researchers found that the blood reacted with some 1,000 autoantibodies present in the microarrays.

While regular antibodies are produced by the immune system in response to viruses and other pathogens, autoantibodies are produced by the immune system in response to the body's own proteins, said senior study author Robert Nagele, founder of Durin Technologies, Inc., which is designed to commercialize diagnostic tools for neurodegenerative diseases such as Alzheimer's. He is also a professor of medicine at the University of Medicine and Dentistry of New Jersey.

But no one is sure what exactly autoantibodies do. One theory is that they are involved with clearing debris, Nagele said.

Researchers used a sophisticated computer analysis to further narrow the test to 10 autoantibodies that, when present, could predict which patients had Alzheimer's and which didn't. They also found that the test predicted who had Alzheimer's and who had Parkinson's -- another neurodegenerative disease -- with 86 percent accuracy.

"We know we can detect Alzheimer's disease in people who have been diagnosed, but the real exciting question is if it's possible for this test [to] detect people when they are pre-symptomatic," Nagele said.

The problem is that even if someone is diagnosed with the brain disease before symptoms appear, there is no cure or treatment to stop its relentless progression. Nagele acknowledged this reality, but has said that scientists are working "feverishly" to develop effective treatments.

"Although there are no treatments now, we are always hopeful one will come soon. If and when such a treatment becomes available, we know early treatment is always better than later," Nagele said. "It's hard to correct damage that already exists. So it would be wonderful to detect people several years before they have symptoms so we can slow down or halt the progression of the disease."

Currently, Alzheimer's is diagnosed after people start having memory problems or other unusual changes in behavior. They undergo a detailed medical interview, a memory assessment test and sometimes an MRI to look for brain shrinkage, Nagele said.

Nagele is seeking a commercial partner and will seek U.S. Food and Drug Administration approval to market the test for use in diagnosing Alzheimer's in the upcoming months, he said.

The study was funded by an investment in Durin Technologies by the Foundation Venture Capital Group LLC, a New Jersey Health Foundation affiliate that invests in start-up companies founded by researchers at UMDNJ. Co-author Eric Nagele is also a paid consultant to Durin and co-author Benjamin Belinka is Durin's CEO.

Discussing the Alzheimer's test, Buchman noted the research was far from definitive. He pointed out that the average age of the Alzheimer's patients was nearly 80, while the age of the controls was 40. That means researchers did not prove that the autoantibodies were necessarily related to Alzheimer's, but instead could be a product of something else, such as aging.

Thomas Kodadek, a professor of chemistry and cancer biology at The Scripps Research Institute in Jupiter, Fla., raised another criticism. Although researchers found a statistical association between the presence of the autoantibodies and Alzheimer's, he said, the lack of understanding about the purpose of autoantibodies or what they have to do with dementia may make acceptance of such a test by physicians more difficult.

"What a physician would like to know is, here is a marker that is somehow associated with the disease in a way a physician can understand, such as cholesterol and heart disease," he said. "It's not really known what autoantibodies do or why they are there. Most of the proteins that bind these antibodies, they have no known function, and there is no clear mechanistic connection to Alzheimer's."

Kodadek is also working on developing an Alzheimer's blood test that screens for antibodies and is running into similar issues, he said.

"At the end of the day, is it crucial to know what the function of these autoantibodies are? No," Kodadek said. "Even if you don't understand what it does, it could still be an important biomarker. But these things are not black and white markers that are completely unique to Alzheimer's patients, which is ideally what you would like to have."

More information

The U.S. National Institute on Aging has more on Alzheimer's disease.

SOURCES: Robert Nagele, Ph.D., founder, Durin Technologies, Inc., and professor of medicine, University of Medicine and Dentistry of New Jersey; Aron Buchman, M.D., neurologist, Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago; Thomas Kodadek, Ph.D., professor, chemistry & cancer biology, The Scripps Research Institute, Jupiter, Fla.; Aug. 3, 2011, PLoS ONE, online

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