Analytical characteristics of the updated elecsys Abeta42 Gen 2 assay, including comparisons with the Gen 1 assay

Background Cerebrospinal fluid (CSF) biomarker amyloid‐β1–42 (Abeta42), quantified using the Elecsys® Abeta42 (Gen 1) immunoassay, supports diagnosis of Alzheimer’s disease. Compared with Gen1, the updated assay Elecsys Abeta42 CSF II (Gen2) has a higher threshold for biotin interference, extended measuring range, and is re‐standardised according to certified reference Abeta42 peptide ERM‐DA480/‐481/‐482. The new Routine‐Use (RU) pre‐analytical protocol will be introduced with the Gen2 assay (reported separately). Here, we present the analytical performance of the Gen2 assay, including comparisons with Gen1. Method Analytical performance experiments were conducted on cobas e 601 analysers. Precision was investigated according to Clinical and Laboratory Standards Institute EP05‐A3 (21‐day experiment) using seven native and two control samples. For lot and instrument comparisons (cobas e 801 vs e 601), 125 native CSF sample pools were measured in one run. Gen1 and Gen2 were compared in two method comparison (MC) studies: in‐house study: 103 frozen CSF samples were measured in one run; external study (Pre‐analytical study 2): CSF samples from 24 patients with suspected normal pressure hydrocephalus were prospectively collected according to the RU, Roche Trial and BioFINDER protocols. MC was based on mean concentrations obtained from 3–4 aliquots per patient. Aliquot‐aliquot variability was compared for each protocol. MC analyses included calculation of Pearson’s correlation (r) and Passing‐Bablok regression fit. Result Precision analysis provided within‐run variability of