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

Research output: Contribution to journalArticle

150 Scopus citations

Abstract

The adaptive immune system is thought to be a rich source of protein biomarkers, but diagnostically useful antibodies remain unknown for a large number of diseases. This is, in part, because the antigens that trigger an immune response in many diseases remain unknown. We present here a general and unbiased approach to the identification of diagnostically useful antibodies that avoids the requirement for antigen identification. This method involves the comparative screening of combinatorial libraries of unnatural, synthetic molecules against serum samples obtained from cases and controls. Molecules that retain far more IgG antibodies from the case samples than the controls are identified and subsequently tested as capture agents for diagnostically useful antibodies. The utility of this method is demonstrated using a mouse model for multiple sclerosis and via the identification of two candidate IgG biomarkers for Alzheimer's disease.

Original languageEnglish (US)
Pages (from-to)132-142
Number of pages11
JournalCell
Volume144
Issue number1
DOIs
StatePublished - Jan 7 2011

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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