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

INTRODUCTION: Cerebrospinal fluid (CSF) concentration of amyloid β peptide (Aβ42) is a key biomarker for Alzheimer’s disease (AD), reflecting brain amyloidosis. Reference materials based on human CSF were certified for the mass concentration of Aβ42. They are intended to be used by in vitro diagnostics manufacturers to calibrate their diagnostic assays for Aβ42. METHODS: The three certified reference materials (CRMs), ERM-DA480/IFCC, ERM-DA481/IFCC and ERM-DA482/IFCC, were prepared at three concentration levels and characterised using isotope dilution mass spectrometry methods. Roche, EUROIMMUN, and Fujirebio utilized the three CRMs to re-calibrate their immunoassays. RESULTS: The certified Aβ42 mass concentrations in ERM-DA480/IFCC, ERM-DA481/IFCC and ERM-DA482/IFCC are 0.45, 0.72 and 1.22 µg/L, respectively, with expanded uncertainties (k = 2) of 0.07, 0.11 and 0.18 µg/L, respectively. Before recalibration, a good correlation (Pearson’s r > 0.97), yet large biases were observed between results from different commercial assays. After re-calibration the between assay bias was reduced to < 5 %. DISCUSSION: The Aβ42 CRMs can ensure the comparability of results between methods and across platforms for the measurement of CSF Aβ42. This may serve as the basis for the introduction of uniform cut-off levels across assays.

BOULO Sébastien;  KUHLMANN Julia;  ANDREASSON Ulf;  BRIX Britta;  VENKATARAMAN Iswariya;  HERBST Victor;  RUTZ Sandra;  MANUILOVA Ekaterina;  VANDIJCK Manu;  DEKEYSER Filip;  BJERKE Maria;  PANNEE Josef;  CHAROUD-GOT Jean;  AUCLAIR Guy;  MAZOUA Stephane;  PINSKI Gregor;  TRAPMANN Stefanie;  SCHIMMEL Heinz;  EMONS Hendrik;  QUAGLIA Milena;  PORTELIUS Erik;  KORECKA Magdalena;  SHAW Leslie;  LAME Mary;  CHAMBERS Erin;  VANDERSTICHELE Hugo;  STOOPS Erik;  LEINENBACH Andreas;  BITTNER Tobias;  JENKINS Rand;  KOSTANJAVECKI Vesna;  LEWCZUK Piotr;  GOBOM Johan;  ZETTERBERG Henrik;  ZEGERS Ingrid;  BLENNOW Kaj; 

2020-11-13

ELSEVIER SCIENCE INC

JRC120079

1552-5260 (online),   

https://alz-journals.onlinelibrary.wiley.com/doi/10.1002/alz.12145,    https://publications.jrc.ec.europa.eu/repository/handle/JRC120079,   

10.1002/alz.12145 (online),