A Luminex Assay Detects Amyloid β Oligomers in Alzheimer's Disease Cerebrospinal Fluid

Amyloid beta (a beta) protein assembles into larger protein aggregates during the pathogenesis of Alzheimer's disease (AD) and there is increasing evidence that soluble a beta oligomers are a critical pathologic species. Diagnostic evaluations rely on the measurement of increased tau and decreased a beta 42 in the cerebrospinal fluid (CSF) from AD patients and evidence for oligomeric a beta in patient CSF is conflicting. In this study, we have adapted a monoclonal single antibody sandwich ELISA assay to a Luminex platform and found that this assay can detect oligomerized a beta 42 and sAPP alpha fragments. We evaluated oligomeric a beta reactivity in 20 patients with AD relative to 19 age matched controls and compared these values with a commercially available Alzbio3 kit that detects tau, phosphorylated tau and a beta 42 on the same diagnostic platform. We found that CSF samples of patients with AD had elevated a beta oligomers compared to control subjects (p < 0.05) and the ratio of a beta oligomers to a beta 42 was also significantly elevated (p < 0.0001). Further research to develop high sensitivity analytical platforms and rigorous methods of developing stable assay standards will be needed before the analysis of oligomeric a beta becomes a routine diagnostic assay for the evaluation of late onset AD patients.