Author(s): Bruggink, K.A.; Jongbloed, W.; Biemans, E.A.L.M.; Veerhuis, R.; Claassen, J.A.H.R. ; Kuiperij, H.B. ; Verbeek, M.M.
Amyloid-beta (Abeta) deposits are important pathological hallmarks of Alzheimer's disease (AD). Abeta 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 Abeta 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 Abeta 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 Abeta oligomer concentration was significantly increased in AD compared with nondemented controls. Abeta 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 Abeta oligomers in human body fluids.