Test might help catch Alzheimer's in early stages

WASHINGTON -- A highly sensitive new test could lead to a different way to diagnose people with Alzheimer's disease, possibly helping find the illness in its early stages when there might be time for treatment.

While as many as 4 million Americans are thought to suffer from the memory-destroying illness, the only way to diagnose it definitively is by studying brain tissue during an autopsy.

It is important to have some way to diagnose the disease while the patient is still alive, especially during its early stages, so experimental treatments can be evaluated, and to catch it at a time when the disease might be treatable.

Many companies have experimental therapies, he said, "but those therapeutics aren't very good if you can't definitively diagnose and follow a disease," explained Chad A. Mirkin of Northwestern University, a lead researcher -- along with William L. Klein -- on a team that developed the new test, which can detect small amounts of proteins in spinal fluid.

The team's findings are reported in today's issue of Proceedings of the National Academy of Science.

The new test, called a bio-barcode assay, is 100,000 times to 1 million times more sensitive than other available tests, Mirkin said.

It was first used last year in testing for a marker for prostate cancer, and Mirkin said he invited other investigators to suggest subjects for further testing

Klein, also at Northwestern, had done research associating Alzheimer's with a protein in the brain called amyloid-beta-derived diffusable ligand, or ADDL, Mirkin said.

So the research team set out to try to detect ADDL in spinal fluid.

They got samples of the spinal fluid of 30 people, 15 who had Alzheimer's disease and 15 who did not.

The researchers found at least some ADDL in all the patients, which Mirkin said is an indication that everyone may have a baseline level of the protein.

"What was really encouraging," he said, is that the concentration of ADDL increases as the disease gets worse, so the progression of the illness could be followed.

"Do we have a new diagnostic for Alzheimer's?" Mirkin said. "That's a bit premature."

The method needs to be repeated and tested on more patients, he said. Also tests need to be done to see if high levels of ADDL occur in other memory loss diseases.

But, the researchers said in their paper, the work provides a "potential reliable detection method for diagnosing" Alzheimer's disease.

In addition, Mirkin said, the researchers are hoping to use the new test to search for proteins and other chemicals that can offer early diagnoses of other diseases, ranging from cancers to AIDS to mad cow.

ADDLs are small soluble proteins. To detect them the researchers used nanoscale particles that had antibodies specific to ADDL. Some particles were magnetic and some of gold with strings of DNA attached.

The antibodies bind to the ADDL, sandwiching the protein between the two particles. They are then removed from the solution magnetically and the hundreds to thousands of DNA strands attached to the gold particles serve as a barcode because they can be used to label the specific target with standard detection methods.

Dr. Samuel Gandy, who was not part of the research team, said the report is impressive but needs to be repeated with larger numbers of subjects.

If the test can, in fact, correlate the presence of ADDLs with brain function, "this is good news indeed for identifying who is at risk for Alzheimer's and potentially for following the effectiveness of many new anti-amyloid medicines that are now in clinical trials," said Gandy, vice chair of the National Medical and Scientific Advisory Council of the Alzheimer's Association and director of the Farber Institute for Neurosciences at Thomas Jefferson University in Philadelphia.

Stephen Snyder, who directs the National Institute on Aging program studying the causes of Alzheimer's, said the finding has future implications for both diagnosis and treatment of the disease.

"For many years the ADDLs have been thought to be involved in diminishing aspects of cognition and this is proof of principle that they exist and can be found" in spinal fluid, said Snyder, who was not part of the research team.

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