期刊
CLINICAL CHEMISTRY AND LABORATORY MEDICINE
卷 60, 期 2, 页码 207-219出版社
WALTER DE GRUYTER GMBH
DOI: 10.1515/cclm-2021-0651
关键词
Alzheimer's disease; biomarkers; immunoassay; LUMIPULSE; validation
资金
- National Programof Sustainability II (MEYS CR) [LQ1605]
- Ministry ofHealth of the Czech Republic [19-04-00560]
- BIONIC project by ZonMW (Dutch national `Deltaplan for Dementia') [733050822]
- Selfridges Group Foundation
- National Institutes of Health, USA [5R01NS10414702]
- Alzheimerfonden [AF-930934]
- Ahlens-stiftelsen
- Stiftelsen for Gamla tjanarinnor
- Swedish Research Council [2018-02532, 2017-00915]
- European Research Council [681712]
- Swedish State Support for Clinical Research [ALFGBG-720931]
- Alzheimer Drug Discovery Foundation (ADDF), USA [201809-2016862, RDAPB-2018092016615]
- European Union [860197]
- UK Dementia Research Institute at UCL
- Swedish Alzheimer Foundation [AF-742881]
- Hjarnfonden, Sweden [FO2017-0243]
- Swedish Government [ALFGBG-715986]
- European Union Joint Program for Neurodegenerative Disorders [JPND2019-466-236]
- 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
- Alzheimer's Association [NIRG-12-92090, NIRP-12-259245]
- Brain Canada Foundation (CFI) [34874, 33397]
- Fonds de Recherche du Quebec -Sante (FRQS
- Chercheur Boursier) [2020-VICO279314]
- MRC [UKDRI-1003] Funding Source: UKRI
The study evaluated the LUMIPULSE G assays for core cerebrospinal fluid biomarkers and established cutpoints for Alzheimer's disease diagnosis. Results showed strong correlation and reliable analytical performance of the LUMIPULSE G assays.
Objectives The core cerebrospinal fluid (CSF) biomarkers; total tau (tTau), phospho-tau (pTau), amyloid beta 1-42 (A beta 1-42), and the A beta 1-42/A beta 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, beta-amyloid 1-42, and with V-PLEX Plus A beta Peptide Panel 1 (6E10) (Meso Scale Discovery) for A beta 1-42/A beta 1-40, as well as with a LC-MS reference method for A beta 1-42. Intra- and inter-laboratory reproducibility was evaluated for all assays. Clinical cutpoints for A beta 1-42, tTau, and pTau was determined by analysis of three cohorts of clinically diagnosed patients, comprising 651 CSF samples. For the A beta 1-42/A beta 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 beta-amyloid 1-40. The reproducibility (inter-laboratory) CVs ranged between 2.1 and 6.5%, with the highest variation observed for beta-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 beta-amyloid 1-42, and 0.072 for the A beta 1-42/A beta 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.
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