Kinetic analysis of IgG antibodies to beta-amyloid oligomers with surface plasmon resonance.
Surface plasmon resonance was used to investigate the kinetics, affinity, and specificity of binding between anti-Aβ (beta-amyloid) IgG antibodies and oligomeric Aβ. Two factors were needed to accurately characterize the IgG binding kinetics. First, a bivalent model was necessary to properly fit the kinetic association and dissociation sensograms. Second, a high concentration of IgG was necessary to overcome a significant mass transport limitation that existed regardless of oligomer density on the sensor surface. Using high IgG concentrations and bivalent fits, consistent kinetic parameters were found at varying sensor surface ligand densities. A comparison of binding specificity, affinity, and kinetic flux between monoclonal and natural human anti-Aβ IgG antibodies revealed the following findings. First, monoclonal antibodies 6E10 and 4G8 single-site binding affinity is similar between Aβ oligomers and monomers. Second, natural human anti-Aβ IgG binding readily binds Aβ oligomers but does not bind monomers. Third, natural human anti-Aβ IgG binds Aβ oligomers with a higher affinity and kinetic flux than 6E10 and 4G8. Both the current analytical methodology and antibody binding profiles are important for advances in antibody drug development and kinetic biomarker applications for Alzheimer's disease.
Division of Sciences and Mathematics, School of Interdisciplinary Arts and Sciences (IAS), University of Washington, Tacoma, WA 98402, USA.
Amanda C
AC
Crisostomo
Eye Research Institute, Oakland University, Rochester, MI 48309, USA.
Loan
L
Dang
Department of Chemistry, Oakland University, Rochester, MI 48309, USA.
Jyothi L
JL
Digambaranath
Department of Neurology Research, Beaumont Health System, Royal Oak, MI 48073, USA.
Andrea C
AC
Klaver
Department of Neurology Research, Beaumont Health System, Royal Oak, MI 48073, USA.
David A
DA
Loeffler
Division of Sciences and Mathematics, School of Interdisciplinary Arts and Sciences (IAS), University of Washington, Tacoma, WA 98402, USA.
Jeremiah J
JJ
Payne
Department of Neurology Research, Beaumont Health System, Royal Oak, MI 48073, USA.
Lynnae M
LM
Smith
Department of Chemistry, Oakland University, Rochester, MI 48309, USA.
Adam L
AL
Yokom
Division of Sciences and Mathematics, School of Interdisciplinary Arts and Sciences (IAS), University of Washington, Tacoma, WA 98402, USA. Electronic address: jfinke@u.washington.edu.
John M
JM
Finke
D016229:Amyloid beta-Peptides / Q000737:chemistry / Q000276:immunology*; D000915:Antibody Affinity; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology*; D007700:Kinetics; D012995:Solubility; D020349:Surface Plasmon Resonance
D016229:Amyloid beta-Peptides; D007074:Immunoglobulin G
Antibody; Beta-amyloid; Binding kinetics; Mass transport; Soluble oligomer; Surface plasmon resonance