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Detection of a biomarker for Alzheimer's disease from synthetic and clinical samples using a nanoscale optical biosensor
Journal article

Detection of a biomarker for Alzheimer's disease from synthetic and clinical samples using a nanoscale optical biosensor

Amanda J Haes, Lei Chang, William L Klein and Richard P Van Duyne
Journal of the American Chemical Society, Vol.127(7), pp.2264-2271
02/23/2005
DOI: 10.1021/ja044087q
PMID: 15713105

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Abstract

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.
Ligands Biomarkers - metabolism Surface Plasmon Resonance Antibodies - metabolism Nanotechnology - methods Humans Biomarkers - analysis Antigens - metabolism Alzheimer Disease - cerebrospinal fluid Brain - metabolism Peptide Fragments - immunology Alzheimer Disease - metabolism Amyloid beta-Peptides - metabolism Amyloid beta-Peptides - analysis Amyloid beta-Peptides - cerebrospinal fluid Antibodies - immunology Antibody Formation Amyloid beta-Peptides - immunology Antigens - immunology Biosensing Techniques - methods Biomarkers - cerebrospinal fluid

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