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 (Aβ₄₂ ). They are intended to be used to calibrate 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 characterized using isotope dilution mass spectrometry methods. Roche, EUROIMMUN, and Fujirebio used 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 re-calibration, 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 equivalence of results between methods and across platforms for the measurement of Aβ₄₂ .

Keywords: Alzheimer's disease; amyloid beta peptide; certified reference material; commercial immunoassays.