Antibody Biomarkers Identified for Alzheimer's Disease

This new approach for the discovery of antibody biomarkers required no knowledge of the specificity of the immune response. An array of random synthetic molecules to pinpoint disease-associated antibodies was used instead of putative antigens.

Scientists at the Scripps Research Institute (Jupiter, FL, USA) used combinatorial library of unnatural, synthetic molecules that might serendipitously mimic the antibody-binding site of the primary antigen. The premise is that these synthetic molecules, termed peptoids, can form shapes that cannot be formed by unmodified biomolecules. Through mimicry, then, peptoids might be able to pinpoint antibodies that are important to the disease process and thus aid in the discovery of biomarkers.

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

The investigators then examined serum samples from 18 humans, 6 with Alzheimer's, 6 individuals with Parkinson's disease, and 6 healthy participants. 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, suggesting that there are at least two candidate biomarkers for Alzheimer's.

Thomas Kodadek, PhD, a professor at Scripps, said, "The plan is to test the method now in the context of diseases, such as pancreatic cancer, where it is clear that early diagnosis could have significant implications for patient survival. It is possible that antibody-based tests might identify such cancers years before they could be detected otherwise. If those antibodies and the natural antigens that they recognize could be found using the new technology, it might even aid the development of new and more effective cancer vaccines designed to bolster the body's natural defenses against the disease." The study was published in January 2011 in the journal Cell.

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