title: Identification of candidate IgG biomarkers for Alzheimer's disease via combinatorial library screening.
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.
authors.affiliation: Opko Health Laboratories, Jupiter, FL 33458, USA.
authors.forename: M Muralidhar
authors.initials: MM
authors.lastname: Reddy
authors.forename: Rosemary
authors.initials: R
authors.lastname: Wilson
authors.forename: Johnnie
authors.initials: J
authors.lastname: Wilson
authors.forename: Steven
authors.initials: S
authors.lastname: Connell
authors.forename: Anne
authors.initials: A
authors.lastname: Gocke
authors.forename: Linda
authors.initials: L
authors.lastname: Hynan
authors.forename: Dwight
authors.initials: D
authors.lastname: German
authors.forename: Thomas
authors.initials: T
authors.lastname: Kodadek
mesh_terms: D000544:Alzheimer Disease / Q000175:diagnosis*; D000818:Animals; D000906:Antibodies; D015415:Biomarkers / Q000378:metabolism; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000175:diagnosis; D006801:Humans; D007074:Immunoglobulin G; D051379:Mice; D019151:Peptide Library
chemical_list: D000906:Antibodies; D015415:Biomarkers; D007074:Immunoglobulin G; D019151:Peptide Library