An ultra‐sensitive immunoassay detects and quantifies soluble Aβ oligomers in human plasma

Abstract Introduction Evidence strongly suggests that soluble oligomers of amyloid beta protein (oAβ) help initiate the pathogenic cascade of Alzheimer's disease (AD). To date, there have been no validated assays specific for detecting and quantifying oAβ in human blood. Methods We developed an ultrasensitive oAβ immunoassay using a novel capture antibody (71A1) with N‐terminal antibody 3D6 for detection that specifically quantifies soluble oAβ in the human brain, cerebrospinal fluid (CSF), and plasma. Results Two new antibodies (71A1; 1G5) are oAβ‐selective, label Aβ plaques in non‐fixed AD brain sections, and potently neutralize the synaptotoxicity of AD brain‐derived oAβ. The 71A1/3D6 assay showed excellent dilution linearity in CSF and plasma without matrix effects, good spike recovery, and specific immunodepletion. Discussion We have created a sensitive, high throughput, and inexpensive method to quantify synaptotoxic oAβ in human plasma for analyzing large cohorts of aged and AD subjects to assess the dynamics of this key pathogenic species and response to therapy.