TY - JOUR
T1 - Amyloid-beta oligomer detection by ELISA in cerebrospinal fluid and brain tissue
AU - Bruggink, K.A.
AU - Jongbloed, W.
AU - Biemans, E.A.L.M.
AU - Veerhuis, R.
AU - Claassen, J.A.H.R.
AU - Kuiperij, H.B.
AU - Verbeek, M.M.
PY - 2013
Y1 - 2013
N2 - Amyloid-β (Aβ) deposits are important pathological hallmarks of Alzheimer's disease (AD). Aβ aggregates into fibrils; however, the intermediate oligomers are believed to be the most neurotoxic species and, therefore, are of great interest as potential biomarkers. Here, we have developed an enzyme-linked immunosorbent assay (ELISA) specific for Aβ oligomers by using the same capture and (labeled) detection antibody. The ELISA predominantly recognizes relatively small oligomers (10-25 kDa) and not monomers. In brain tissue of APP/PS1 transgenic mice, we found that Aβ oligomer levels increase with age. However, for measurements in human samples, pretreatment to remove human anti-mouse antibodies (HAMAs) was required. In HAMA-depleted human hippocampal extracts, the Aβ oligomer concentration was significantly increased in AD compared with nondemented controls. Aβ oligomer levels could also be quantified in pretreated cerebrospinal fluid (CSF) samples; however, no difference was detected between AD and control groups. Our data suggest that levels of small oligomers might not be suitable as biomarkers for AD. In addition, we demonstrate the importance of avoiding HAMA interference in assays to quantify Aβ oligomers in human body fluids. © 2012 Elsevier Inc. All rights reserved.
AB - Amyloid-β (Aβ) deposits are important pathological hallmarks of Alzheimer's disease (AD). Aβ aggregates into fibrils; however, the intermediate oligomers are believed to be the most neurotoxic species and, therefore, are of great interest as potential biomarkers. Here, we have developed an enzyme-linked immunosorbent assay (ELISA) specific for Aβ oligomers by using the same capture and (labeled) detection antibody. The ELISA predominantly recognizes relatively small oligomers (10-25 kDa) and not monomers. In brain tissue of APP/PS1 transgenic mice, we found that Aβ oligomer levels increase with age. However, for measurements in human samples, pretreatment to remove human anti-mouse antibodies (HAMAs) was required. In HAMA-depleted human hippocampal extracts, the Aβ oligomer concentration was significantly increased in AD compared with nondemented controls. Aβ oligomer levels could also be quantified in pretreated cerebrospinal fluid (CSF) samples; however, no difference was detected between AD and control groups. Our data suggest that levels of small oligomers might not be suitable as biomarkers for AD. In addition, we demonstrate the importance of avoiding HAMA interference in assays to quantify Aβ oligomers in human body fluids. © 2012 Elsevier Inc. All rights reserved.
U2 - https://doi.org/10.1016/j.ab.2012.09.014
DO - https://doi.org/10.1016/j.ab.2012.09.014
M3 - Article
C2 - 23022042
SN - 0003-2697
VL - 433
SP - 112
EP - 120
JO - Analytical biochemistry
JF - Analytical biochemistry
IS - 2
ER -
