Advances Made Toward Alzheimer's Blood Test

Study Shows Synthetic Molecules May Help Detect Alzheimer's, MS, and Other Diseases

By Salynn Boyles
WebMD Health News

Reviewed by Laura J. Martin, MD

Jan. 6, 2011 -- Molecules developed in the lab to seek out antibodies associated with disease could lead to simple blood tests for Alzheimer's, multiple sclerosis, and a host of other diseases, researchers say.

The new experimental technology relies on thousands of synthetic molecules known as peptoids to search for antibodies that occur in response to disease.

The hope is that the man-made molecules will lead to tests to identify diseases like Alzheimer's and cancer long before symptoms occur, says Thomas Kodadek, PhD, who is a professor of chemistry and cancer biology at the Scripps Research Institute in Jupiter, Fla.

A New Way to Search for Disease

Research to identify biomarkers that can be used to screen for disease has largely focused on proteins that are elevated or not elevated for a particular disease state.

But Kodadek says this has proven to be very difficult because the proteins are hard to find and not very stable.

Another approach is to look for the antibodies produced by the immune system in response to harmful molecules, or antigens, linked to disease.

Most of this research has focused on identifying disease-specific antigens, which has also proven to be a major problem, Kodadek says.

"We took a different approach," he tells WebMD. "Our approach eliminates the need to know anything about the disease in order to find candidate biomarkers. That is the big breakthrough here."

Using large numbers of peptoids, the researchers conducted random screens of blood taken from animals and humans to search for disease-specific antibodies.

Early studies involved mice with a condition that resembles multiple sclerosis in humans.

Using the technique, Kodadek and colleagues were able to identify several disease-specific peptoid-antibody pairs in the blood of the sick mice that were not present in healthy mice.

In a small, pilot study involving Alzheimer's patients, the researchers identified three peptoid-antibody pairs in the blood of six patients with the age-related dementia that were not present in the blood samples of healthy people or those with Parkinson's disease.

The study appears this week in the journal Cell.

Blood Test for Alzheimer's, Pancreatic Cancer?

Kodadek says his research team has now screened around 300 Alzheimer's patients and the method reliably identified disease in blood samples.

"Many of the patients had very early-stage disease," he says. "There are also early signs that this can detect pre-symptomatic Alzheimer's disease, but we aren't quite there yet."

The technique is currently too complicated to perform outside the laboratory, but the researchers are working on simplifying it to make it easy to perform in a doctor's office.

Kodadek is now developing the technology for the Miami-based medical research company Opko Health Inc., which hopes to develop and market blood tests for a wide range of diseases.

He says his research team has now identified four peptoids that appear to be specific for pancreatic cancer and three that appear specific for non-small-cell lung cancer.

Ralph Nixon, MD, who serves on the scientific advisory council for the Alzheimer's Association, says while the research sounds promising it is still in the very early stages.

Nixon also directs the Center of Excellence on Brain Aging at New York University Langone Medical Center.

It is now possible to determine which patients with early cognitive impairment will develop Alzheimer's by testing spinal fluid, but Nixon calls a blood test the Holy Grail for diagnosing the disease.

Other researchers are also working to develop a blood test, but Nixon says he has seen nothing to suggest such a test will be a reality in the near future.

"We have seen glimpses that it may happen, but not the hard data to show that we are actually close," he tells WebMD.

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SOURCES: Muralidhar, M. Cell, Jan. 7, 2011; vol 144: pp 132-142.Thomas J. Kodadek, PhD, professor of chemistry and cancer biology, Scripps Research Institute, Jupiter, Fla.Ralph Nixon, MD, director, Center of Excellence on Brain Aging, New York University Langone Medical Center.News release, Cell Press.

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