Method comparison study of the Elecsys® β-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-β (1-42; Aβ42), can provide high diagnostic accuracy. Several immunoassays are available for Aβ42 quantitation, but standardisation across assays remains an issue. We compared the Elecsys® β-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® β-Amyloid (1-42) CSF assay versus: INNOTEST® β-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® β-Amyloid (1-42) CSF and comparator assays: INNOTEST® β-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® β-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 Aβ42 cut-off to detect amyloid pathology.

Keywords: Alzheimer's disease; Amyloid-β peptide; Biomarker; Cerebrospinal fluid; Correlation; Immunoassay.