Commutability of the certified reference materials for the standardization of β-Amyloid 1-42 assay in human cerebrospinal fluid: Lessons for tau and β-Amyloid 1-40 measurements

Abstract

The core Alzheimer's disease cerebrospinal fluid (CSF) biomarkers total tau (T-Tau), phosphorylated tau (P-Tau), β-Amyloid 1-42 (Aβ42) and β-Amyloid 1-40 (Aβ40) are increasing in importance and are now part of the research criteria for the diagnosis of the disease. The main aim of this study is to evaluate whether a set of certified reference materials (CRMs) are commutable for Aβ42 and to serve as a feasibility study for the other markers. This property is a prerequisite for the establishment of CRMs which will then be used by manufacturers to calibrate their assays against. Once the preanalytical factors have been standardized and proper selection criteria are available for subject cohorts this harmonization between methods will allow for universal cut-offs to be determined. Thirty-four individual CSF samples and three different CRMs where analyzed for T-Tau, P-Tau, Aβ42 and Aβ40, using up to seven different commercially available methods. For Aβ40 and Aβ42 a mass spectrometry-based procedure was also employed. There were strong pairwise correlations between the different methods (Spearman's ρ>0.92) for all investigated analytes and the CRMs were not distinguishable from the individual samples. This study shows that the CRMs are commutable for the different assays for Aβ42. For the other analytes the results show that it would be feasible to also produce CRMs for these. However, additional studies are needed as the concentration interval for the CRMs were selected based on Aβ42 concentrations only and did in general not cover satisfactory large concentration intervals for the other analytes.