Simultaneous Measurement of β-Amyloid(1–42), Total Tau, and Phosphorylated Tau (Thr181) in Cerebrospinal Fluid by the xMAP Technology

Background: To simultaneously study several biomarkers for Alzheimer disease (AD), we used the xMAP™ technology to develop and evaluate a multiparametric bead-based assay for quantification of β-amyloid(1–42) [Aβ(1–42)], total tau (T-TAU), and hyperphosphorylated tau [P-TAU(181P)] in cerebrospinal fluid (CSF). Methods: We compared the new multianalyte assay format with established ELISA techniques for the same proteins. We then performed a clinical study using CSF samples from patients with AD or mild cognitive impairment with progression to AD, healthy controls, and patients with other neurologic disorders. Results: The INNO-BIA AlzBio3 selectively and specifically measured Aβ(1–42), T-TAU, and P-TAU(181P) in the CSF. The new assay format had intra- and interassay CVs <10% for all analytes, even at low concentrations. The measurement range of the new assay was 3 to 4 logs compared with 1 to 2 logs for ELISAs. By plotting the mean of the values obtained in ELISA and the xMAP technology against the difference, we found that a correction factor could be used to convert xMAP results to ELISA values. The clinical study demonstrated that the new multiparametric assay could accurately distinguish patients with AD from patients with other neurologic disorders or control patients, with the diagnostic accuracy reaching recommended consensus criteria for specificity and sensitivity. Conclusion: The new multiparametric method may be able to replace the corresponding ELISA methods.