First amyloid β1‐42 certified reference material for re‐calibrating commercial immunoassays

Abstract

Introduction: Reference materials based on human cerebrospinal fluid were certified for the mass concentration of amyloid beta (Aβ)1-42 (Aβ 42). They are intended to be used to calibrate diagnostic assays for Aβ 42. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

2020 update on the clinical validity of cerebrospinal fluid amyloid, tau, and phospho-tau as biomarkers for Alzheimer’s disease in the context of a structured 5-phase development framework

“…Though a mass spectrometry-based method of quantification for T-tau has been developed [194], an important and as yet unmet prerequisite for the wider use of T-tau and P-tau measurements is the current lack of CRMs for assay standardization [47]. Advances similar to those for Aβ42 (i.e., the development and implementation of certified reference materials and methods) [22,195] will hopefully soon follow for tau [196].…”

“…The first secondary aim of phase 2 addresses optimization of the operating procedures and assessment of the reproducibility of the assay within and between laboratories. The secondary aim 1 of phase 2 is now fully achieved for CSF Aβ42, for which certified reference methods and materials for assay standardization are in place [22]. Similar work is ongoing but has not yet been completed for CSF tau biomarkers.…”

“…Concentrations of CSF AD biomarkers can be affected by operator-influenced preanalytical variables [23,24], including sampling materials and methodology as well as handling and storage procedures [23,[25][26][27][28][29][30][31][32]. The consensus within the field is that together with appropriate use criteria [33], certified reference methods and materials [22], and high precision measurements [34], the standardization of these factors will reduce variability and increase the diagnostic accuracy of these measures; this, in turn, will facilitate widespread use of CSF AD biomarkers in both clinical research and routine clinical practice [27,35]. Recent work addressing the influence of preanalytical factors on both CSF Aβ42 and Aβ40 has provided an initial protocol covering temperature and storage time, centrifugation, sample mixing, and blood contamination [35].…”

“…Similar automated platforms for AD biomarkers have since been launched, including those from Euroimmun [50], and Fujirebio (LUMIPULSE®) [51][52][53][54], and have shown superior performance in the QC program [44]. The certified reference materials for Aβ42 have now been fully implemented and will allow for full standardization of all commercially available CSF Aβ42 methods [22]. Work to develop certified reference methods and materials for T-tau and P-tau is ongoing, under the auspices of the International Federation of Clinical Chemistry and Laboratory Medicine and the Global Biomarker Standardization Consortium.…”

“…In addition, the LUMIPULSE® assay, that provides a quantitative result for an analyte within 35 min, demonstrates an Aβ42/Aβ40 cutoff of 0.068 for an AD diagnoses but is also validated against Amyloid PET [89]. These methods are now being standardized to each other in terms of the absolute CSF Aβ42 concentration they deliver [22].…”