title: Amyloid-β oligomer detection by ELISA in cerebrospinal fluid and brain tissue.
abstract: 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.
authors.affiliation: Department of Neurology, Department of Laboratory Medicine, Donders Institute for Brain, Cognition and Behaviour, Radboud Alzheimer Centre, Radboud University Medical Centre, 6500 HB Nijmegen, The Netherlands.
authors.forename: Kim A
authors.initials: KA
authors.lastname: Bruggink
authors.forename: Wesley
authors.initials: W
authors.lastname: Jongbloed
authors.forename: Elisanne A L M
authors.initials: EA
authors.lastname: Biemans
authors.forename: Rob
authors.initials: R
authors.lastname: Veerhuis
authors.forename: Jurgen A H R
authors.initials: JA
authors.lastname: Claassen
authors.forename: H Bea
authors.initials: HB
authors.lastname: Kuiperij
authors.forename: Marcel M
authors.initials: MM
authors.lastname: Verbeek
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid* / Q000235:genetics; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid* / Q000235:genetics; D000818:Animals; D001923:Brain Chemistry; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods / Q000592:standards; D005260:Female; D006624:Hippocampus / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D008875:Middle Aged; D012680:Sensitivity and Specificity
chemical_list: D016229:Amyloid beta-Peptides