2026-04-14T07:15:47Zhttps://recercat.cat/oai/request

oai:recercat.cat:2072/4692172025-10-10T06:03:36Zcom_2072_98col_2072_378192

urn:hdl:2072/469217 Validation of the LUMIPULSE automated immunoassay for the measurement of core AD biomarkers in cerebrospinal fluid Gobom, Johan Parnetti, Lucilla Rosa-Neto, Pedro Vyhnalek, Martin Gauthier, Serge Cataldi, Samuela Lerch, Ondrej Laczo, Jan Cechova, Katerina Clarin, Marcus Benet, Andrea L. Pascoal, Tharick A. Rahmouni, Neserine Vandijck, Manu Huyck, Else Le Bastard, Nathalie Stevenson, Jenna Chamoun, Mira Alcolea, Daniel Lleó, Alberto Andreasson, Ulf Verbeek, Marcel M. Bellomo, Giovanni Rinaldi, Roberta Ashton, Nicholas J. Zetterberg, Henrik Sheardova, Katerina Hort, Jakub Blennow, Kaj Universitat Autònoma de Barcelona Alzheimer's disease Biomarkers Immunoassay LUMIPULSE Validation Altres ajuts: Swedish Research Council (#2017-00915); Alzheimer Drug Discovery Foundation (ADDF), USA (#RDAPB-201809-2016615); Swedish Alzheimer Foundation (#AF-742881); Hjärnfonden, Sweden (#FO2017-0243); Swedish State Under the Agreement Between the Swedish Government and the County Councils, the ALF-Agreement (#ALFGBG-715986); National Program of Sustainability II (MEYS CR); Ministry of Health of the Czech Republic (grant no. 19-04-00560); ZonMW (part of the Dutch national 'Deltaplan for Dementia'; Selfridges Group Foundation; National Institutes of Health, USA (grant number 5R01NS104147-02); Alzheimerfonden (AF-930934); Åhléns-stiftelsen; Stiftelsen för Gamla tjänarinnor; Canadian Institutes of Health Research (CIHR) (MOP-11-51-31; RFN 152985, 159815, 162303); Canadian Consortium of Neurodegeneration and Aging (CCNA; MOP-11-51-31 -team 1); Weston Brain Institute, the Alzheimer's Association (NIRG-12-92090, NIRP-12-259245); Brain Canada Foundation (CFI Project 34874; 33397); Fonds de Recherche du Québec - Santé (FRQS; Chercheur Boursier, 2020-VICO-279314); Wallenberg Scholar supported by grants, Swedish Research Council (#2018-02532); Swedish State Support for Clinical Research (#ALFGBG-720931); Alzheimer Drug Discovery Foundation (ADDF), USA (#201809-2016862); Dementia Research Institute at UCL. Objectives: The core cerebrospinal fluid (CSF) biomarkers; total tau (tTau), phospho-tau (pTau), amyloid β 1-42 (Aβ 1-42), and the Aβ 1-42/Aβ 1-40 ratio have transformed Alzheimer's disease (AD) research and are today increasingly used in clinical routine laboratories as diagnostic tools. Fully automated immunoassay instruments with ready-to-use assay kits and calibrators has simplified their analysis and improved reproducibility of measurements. We evaluated the analytical performance of the fully automated immunoassay instrument LUMIPULSE G (Fujirebio) for measurement of the four core AD CSF biomarkers and determined cutpoints for AD diagnosis. Methods: Comparison of the LUMIPULSE G assays was performed with the established INNOTEST ELISAs (Fujirebio) for hTau Ag, pTau 181, β-amyloid 1-42, and with V-PLEX Plus Aβ Peptide Panel 1 (6E10) (Meso Scale Discovery) for Aβ 1-42/Aβ 1-40, as well as with a LC-MS reference method for Aβ 1-42. Intra- and inter-laboratory reproducibility was evaluated for all assays. Clinical cutpoints for Aβ 1-42, tTau, and pTau was determined by analysis of three cohorts of clinically diagnosed patients, comprising 651 CSF samples. For the Aβ 1-42/Aβ 1-40 ratio, the cutpoint was determined by mixture model analysis of 2,782 CSF samples. Results: The LUMIPULSE G assays showed strong correlation to all other immunoassays (r>0.93 for all assays). The repeatability (intra-laboratory) CVs ranged between 2.0 and 5.6%, with the highest variation observed for β-amyloid 1-40. The reproducibility (inter-laboratory) CVs ranged between 2.1 and 6.5%, with the highest variation observed for β-amyloid 1-42. The clinical cutpoints for AD were determined to be 409 ng/L for total tau, 50.2 ng/L for pTau 181, 526 ng/L for β-amyloid 1-42, and 0.072 for the Aβ 1-42/Aβ 1-40 ratio. Conclusions: Our results suggest that the LUMIPULSE G assays for the CSF AD biomarkers are fit for purpose in clinical laboratory practice. Further, they corroborate earlier presented reference limits for the biomarkers. 2022 Article European Commission 681712 European Commission 860197 European Commission JPND2019-466-236 Clinical Chemistry and Laboratory Medicine ; Vol. 60 Núm. 2 (january 2022), p. 207-219 open access Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original. https://creativecommons.org/licenses/by/4.0/