Immune molecules specific to Alzheimer’s disease can be detected in a new type of blood test developed by researchers at The Scripps Research Institute, Florida campus, according to an article published in the journal Cell. The authors say this novel technology could be used in the development of biomarkers for various hard-to-detect diseases, such as cancer.

The authors explain that antigens have traditionally been necessary for antibody biomarkers to be discovered. An antigen is a substance that triggers an immune response, such as the protein from a bacterium or virus. It had been impossible to identify an antibody without first finding out what the antigen that triggered its production was. An antibody is a type of targeted immune molecule.

In this latest study, synthetic molecules instead of antigens were used to successfully detect signs of disease in the blood samples of patients. These synthetic compounds can be easily altered and produced rapidly in fairly large amounts at low cost.

The study was led by Scripps Research Professor Thomas Kodadek, Ph.D.

James M. Anderson, M.D., Ph.D., director of the National Institutes of Health (NIH) Division of Program Coordination, Planning, and Strategic Initiatives, said:

“Dr. Kodadek has conceived of a new approach for identifying antibody biomarkers of human disease that bypasses the conventional, but difficult, step of identifying the natural antigens or antigen mimics. The results in the paper suggest great potential for using this approach to rapidly develop diagnostic biomarkers for a variety of significant human diseases. Such boldness to challenge conventional paradigms to achieve important scientific advances is a hallmark of the NIH Director’s Pioneer Award Program, which supported much of this research.”

Prof. Kodadek said:

“This study essentially puts an end to the notion that the only way to pull a potentially useful antibody from blood samples is with a specific antigen. Because the antigen identification problem has proven to be so difficult, we decided to take it out of the equation.”

Kodadek and team used comparative screening of combination libraries of peptoids (synthetic molecules) against serum samples from mice with MS (multiple sclerosis) like symptoms, as well as healthy mice. The peptoids that retained more IgG (immunoglobulin) from the blood samples of the sick animals were identified as potential agents for capturing diagnostically useful molecules. The team says this worked successfully.

They then examined serum samples from 18 humans – six with Alzheimer’s, six healthy participants, and six individuals with Parkinson’s disease. They identified three peptoids that captured three times the IgG antibody levels in all the Alzheimer’s patients than the controls or Parkinson’s patients. Two of the peptoids were found to bind the same IgG antibodies, while the third binds different antibodies – meaning there are at least two candidate biomarkers for Alzheimer’s.

Kodadek said:

“We use these peptoids as a lure to capture the IgG antibodies. Some of these synthetic molecules recognize the antigen-binding sites of disease-specific antibodies well enough to pull them from blood samples, although they almost certainly don’t bind as well as the native antigens. This ability should make it possible to short circuit the discovery of the natural antigens.”

Put simply, the technology involves using synthetic molecules – peptoids – to seek out disease-specific antibodies in the blood.

“Identification of Candidate IgG Biomarkers for Alzheimer’s Disease via Combinatorial Library Screening”
M. Muralidhar Reddy, Rosemary Wilson, Johnnie Wilson, Steven Connell, Anne Gocke, Linda Hynan, Dwight German, Thomas Kodadek
Cell, Volume 144, Issue 1, 132-142, 7 January 2011

Written by Christian Nordqvist