Validation of the LUMIPULSE automated immunoassay for the measurement of core AD biomarkers in cerebrospinal fluid
Gobom, Johan (Clinical Neurochemistry Laboratory. Sahlgrenska University Hospital)
Parnetti, Lucilla (Laboratory of Clinical Neurochemistry. Section of Neurology. University of Perugia)
Rosa-Neto, Pedro (Montreal Neurological Institute)
Vyhnalek, Martin (International Clinical Research Center. St. Anne's University Hospital)
Gauthier, Serge (Montreal Neurological Institute)
Cataldi, Samuela (Laboratory of Clinical Neurochemistry. Section of Neurology. University of Perugia)
Lerch, Ondrej (International Clinical Research Center. St. Anne's University Hospital)
Laczo, Jan (International Clinical Research Center. St. Anne's University Hospital)
Cechova, Katerina (International Clinical Research Center. St. Anne's University Hospital)
Clarin, Marcus (Clinical Neurochemistry Laboratory. Sahlgrenska University Hospital)
Benet, Andrea L. (Translational Neuroimaging Laboratory. McGill Centre for Studies in Aging. McGill University)
Pascoal, Tharick A. (Translational Neuroimaging Laboratory. McGill Centre for Studies in Aging. McGill University)
Rahmouni, Neserine (Translational Neuroimaging Laboratory. McGill Centre for Studies in Aging. McGill University)
Vandijck, Manu (Fujirebio Europe N.V.)
Huyck, Else (Fujirebio Europe N.V.)
Le Bastard, Nathalie (Fujirebio Europe N.V.)
Stevenson, Jenna (Translational Neuroimaging Laboratory. McGill Centre for Studies in Aging. McGill University)
Chamoun, Mira (Translational Neuroimaging Laboratory. McGill Centre for Studies in Aging. McGill University)
Alcolea, Daniel (Institut d'Investigació Biomèdica Sant Pau)
Lleó, Alberto (Institut d'Investigació Biomèdica Sant Pau)
Andreasson, Ulf (Clinical Neurochemistry Laboratory. Sahlgrenska University Hospital)
Verbeek, Marcel M. (Department of Neurology. Radboud Alzheimer Centre. Radboud University Medical Center. Donders Institute for Brain. Cognition and Behaviour)
Bellomo, Giovanni (Laboratory of Clinical Neurochemistry. Section of Neurology. University of Perugia)
Rinaldi, Roberta (Laboratory of Clinical Neurochemistry. Section of Neurology. University of Perugia)
Ashton, Nicholas J. (NIHR Biomedical Research Centre for Mental Health and Biomedical Research Unit for Dementia at South London and Maudsley NHS Foundation)
Zetterberg, Henrik (UCL Institute of Neurology (Regne Unit). UK Dementia Research Institute)
Sheardova, Katerina (First Department of Neurology. Faculty of Medicine. Masaryk University. St. Anne's University Hospital)
Hort, Jakub (First Department of Neurology. Faculty of Medicine. Masaryk University. St. Anne's University Hospital)
Blennow, Kaj (Clinical Neurochemistry Laboratory. Sahlgrenska University Hospital)
Universitat Autònoma de Barcelona

Data:	2022
Resum:	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.
Ajuts:	European Commission 681712 European Commission. Horizon 2020 860197 European Commission JPND2019-466-236
Nota:	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.
Drets:	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.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	Alzheimer's disease ; Biomarkers ; Immunoassay ; LUMIPULSE ; Validation
Publicat a:	Clinical Chemistry and Laboratory Medicine, Vol. 60 Núm. 2 (january 2022) , p. 207-219, ISSN 1437-4331

DOI: 10.1515/cclm-2021-0651
PMID: 34773730

13 p, 1.3 MB

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