Method comparison study of the Elecsys® ß-Amyloid (1-42) CSF assay versus comparator assays and LC-MS/MS.

ABSTRACT

BACKGROUND: Alzheimer's disease (AD) biomarkers, such as cerebrospinal fluid (CSF) amyloid-ß (1-42; Aß42), can provide high diagnostic accuracy. Several immunoassays are available for Aß42 quantitation, but standardisation across assays remains an issue. We compared the Elecsys® ß-Amyloid (1-42) CSF assay with three assays and two liquid chromatography tandem mass spectrometry (LC-MS/MS) methods. METHODS: Three method comparison studies evaluated the correlation between the Elecsys® ß-Amyloid (1-42) CSF assay versus INNOTEST® ß-AMYLOID(1-42) (860 samples) and the Roche Diagnostics-developed LC-MS/MS method (250 samples); INNO-BIA AlzBio3 and the University of Pennsylvania (UPenn)-developed LC-MS/MS method (250 samples); and ADx-EUROIMMUN Beta-Amyloid (1-42) enzyme-linked immunosorbent assay (ELISA) (49 samples). RESULTS: High correlation was demonstrated between Elecsys® ß-Amyloid (1-42) CSF and comparator assays INNOTEST® ß-AMYLOID(1-42) (Spearman's ρ, 0.954); INNO-BIA AlzBio3 (Spearman's ρ, 0.864); ADx-EUROIMMUN Beta-Amyloid (1-42) ELISA (Pearson's r, 0.925). Elecsys® assay and LC-MS/MS measurements were highly correlated Pearson's r, 0.949 (Roche Diagnostics-developed method) and 0.943 (UPenn-developed method). CONCLUSION: Findings from this multicentre evaluation further support use of the Elecsys® ß-Amyloid (1-42) CSF assay to aid AD diagnosis. CSF-based certified reference materials should improve agreement across assays and mass spectrometry-based methods, which is essential to establish a global uniform CSF Aß42 cut-off to detect amyloid pathology.