title: Isolation and characterization of antibody fragments selective for toxic oligomeric tau.
abstract: Oligomeric tau species are important in the onset and progression of Alzheimer's disease (AD), as they are neurotoxic and can propagate tau-tangle pathology. Therefore, reagents that selectively recognize different key morphologies of tau are needed to help define the role of tau in AD and related diseases. We utilized a biopanning protocol that combines the binding diversity of phage-displayed antibody libraries with the powerful imaging capability of atomic force microscopy to isolate single-chain antibody fragments (scFvs) that selectively bind toxic oligomeric tau. We isolated 3 different antibody fragments that bind oligomeric but not monomeric or fibrillar tau. The scFvs differentiate brain tissue homogenates of both 3×TG and tau-AD mice from wild-type mice, detecting oligomeric tau at much earlier ages than when neurofibrillary tangles are typically detected. The scFvs also distinguish human postmortem AD brain tissue from cognitively normal postmortem human brain tissue, demonstrating the potential of this approach for developing biomarkers for early detection and progression of AD.
authors.affiliation: Department of Chemical Engineering, Arizona State University, Tempe, AZ, USA.
authors.forename: Huilai
authors.initials: H
authors.lastname: Tian
authors.affiliation: Oligomerix Inc, Valhalla, NY, USA.
authors.forename: Eliot
authors.initials: E
authors.lastname: Davidowitz
authors.affiliation: Oligomerix Inc, Valhalla, NY, USA.
authors.forename: Patricia
authors.initials: P
authors.lastname: Lopez
authors.affiliation: Department of Chemical Engineering, Arizona State University, Tempe, AZ, USA.
authors.forename: Ping
authors.initials: P
authors.lastname: He
authors.affiliation: Department of Chemical Engineering, Arizona State University, Tempe, AZ, USA.
authors.forename: Philip
authors.initials: P
authors.lastname: Schulz
authors.affiliation: Oligomerix Inc, Valhalla, NY, USA.
authors.forename: James
authors.initials: J
authors.lastname: Moe
authors.affiliation: Department of Chemical Engineering, Arizona State University, Tempe, AZ, USA. Electronic address: sierks@asu.edu.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Sierks
mesh_terms: D000544:Alzheimer Disease / Q000175:diagnosis* / Q000209:etiology* / Q000473:pathology; D000818:Animals; D000906:Antibodies / Q000302:isolation & purification*; D015415:Biomarkers / Q000032:analysis; D001921:Brain / Q000378:metabolism*; D004195:Disease Models, Animal; D006801:Humans; D007135:Immunoglobulin Variable Region / Q000276:immunology* / Q000302:isolation & purification*; D008822:Mice, Transgenic; D019151:Peptide Library; D011108:Polymers; D066329:Protein Aggregates / Q000276:immunology*; D016875:tau Proteins / Q000032:analysis* / Q000276:immunology* / Q000633:toxicity
chemical_list: D000906:Antibodies; D015415:Biomarkers; D007135:Immunoglobulin Variable Region; D019151:Peptide Library; D011108:Polymers; D066329:Protein Aggregates; D016875:tau Proteins
keywords: Alzheimer's disease; Antibody fragments; Biomarker; Brain tissue; Immunotherapy; Oligomeric tau; Phage display; Toxic tau aggregates; scFv