Detection of a biomarker for Alzheimer's disease from synthetic and clinical samples using a nanoscale optical biosensor.
A nanoscale optical biosensor based on localized surface plasmon resonance (LSPR) spectroscopy has been developed to monitor the interaction between the antigen, amyloid-beta derived diffusible ligands (ADDLs), and specific anti-ADDL antibodies. Using the sandwich assay format, this nanosensor provides quantitative binding information for both antigen and second antibody detection that permits the determination of ADDL concentration and offers the unique analysis of the aggregation mechanisms of this putative Alzheimer's disease pathogen at physiologically relevant monomer concentrations. Monitoring the LSPR-induced shifts from both ADDLs and a second polyclonal anti-ADDL antibody as a function of ADDL concentration reveals two ADDL epitopes that have binding constants to the specific anti-ADDL antibodies of 7.3 x 10(12) M(-1) and 9.5 x 10(8) M(-1). The analysis of human brain extract and cerebrospinal fluid samples from control and Alzheimer's disease patients reveals that the LSPR nanosensor provides new information relevant to the understanding and possible diagnosis of Alzheimer's disease.
Haes
Amanda J
AJ
Department of Chemistry, Northwestern University, 2145 Sheridan Road, Evanston, Illinois 60208-3113, USA.
Chang
Lei
L
Klein
William L
WL
Van Duyne
Richard P
RP
D000544:Alzheimer Disease / Q000134:cerebrospinal fluid / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000032:analysis / Q000134:cerebrospinal fluid / Q000276:immunology / Q000378:metabolism*; D000906:Antibodies / Q000276:immunology / Q000378:metabolism; D000917:Antibody Formation; D000941:Antigens / Q000276:immunology / Q000378:metabolism; D015415:Biomarkers / Q000032:analysis / Q000134:cerebrospinal fluid / Q000378:metabolism; D015374:Biosensing Techniques / Q000379:methods*; D001921:Brain / Q000378:metabolism; D006801:Humans; D008024:Ligands; D036103:Nanotechnology / Q000379:methods; D010446:Peptide Fragments / Q000276:immunology; D020349:Surface Plasmon Resonance
D016229:Amyloid beta-Peptides; D000906:Antibodies; D000941:Antigens; D015415:Biomarkers; D008024:Ligands; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42)