The novel methodology used in the test could lead to blood tests for other diseases as well, according to investigators.
Using a technology that relies on thousands of synthetic molecules to search for disease-specific antibodies, researchers have developed a potential method for detecting Alzheimer’s disease with a simple blood test, according to a report in the January 7 issue of Cell.
“If this works in Alzheimer’s disease, it suggests it is a pretty general platform that may work for a lot of different diseases,” said Thomas Kodadek, PhD, Professor of Chemistry and Cancer Biology, Scripps Research Institute in Jupiter, Florida. “Now we need to put it in the hands of disease experts to tackle diseases where early diagnosis is key.”
The method relies on the notion that many diseases lead to the production of modified proteins. At some point, the adaptive immune system might begin to recognize those proteins as foreign and mount a response. If tests could be developed to recognize those disease-specific proteins or the antibodies that recognize them, they could be the basis for early diagnosis. But in most cases, researchers have had little luck identifying those abnormal proteins.
Dr. Kodadek’s team used a large library of randomly selected peptoids to screen for antibodies found in the bloodstream of animals or patients with specific diseases and not in healthy controls. The method is very practical, he said, because it allows for the assembly of enormous chemical libraries with little effort. It also offers a way to “step outside of the usual biological or chemical space” in search of molecules that might just fill the pockets of antibodies playing unknown roles in disease.
As a proof of concept, the researchers started with mice with experimental autoimmune encephalitis. Using a few thousand peptoids, the researchers found a handful that could distinguish blood samples taken from healthy versus sick mice.
The next challenge was to see whether the same method would also work in the case of human Alzheimer’s disease. The method uncovered three peptoids that appear to discriminate between healthy and Alzheimer’s disease blood samples with high accuracy.
Dr. Kodadek said that they have since extended the test to more patients and it appears to be successful. Nevertheless, development of a clinically useful test will depend on further validation. It is possible that the test would not work as reliably in a collection of patients representing different ethnic groups or different forms of dementia, he cautioned. The researchers also need to transition their peptoid technology to a simpler platform better suited for use outside a research laboratory.
It is not entirely clear whether an early test for Alzheimer’s disease would be broadly useful today given that there are no real treatment options, he added. Such a test might initially be most useful to pharmaceutical companies, by allowing them to better identify patients with early Alzheimer’s disease for enrollment into clinical trials.