Validation of the LUMIPULSE automated immunoassay for the measurement of core AD biomarkers in cerebrospinal fluid.
Alzheimer’s disease
LUMIPULSE
biomarkers
immunoassay
validation
Journal
Clinical chemistry and laboratory medicine
ISSN: 1437-4331
Titre abrégé: Clin Chem Lab Med
Pays: Germany
ID NLM: 9806306
Informations de publication
Date de publication:
27 01 2022
27 01 2022
Historique:
received:
01
01
2021
accepted:
02
11
2021
pubmed:
14
11
2021
medline:
26
3
2022
entrez:
13
11
2021
Statut:
epublish
Résumé
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. 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. 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. 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.
Identifiants
pubmed: 34773730
pii: cclm-2021-0651
doi: 10.1515/cclm-2021-0651
doi:
Substances chimiques
Amyloid beta-Peptides
0
Biomarkers
0
Peptide Fragments
0
tau Proteins
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
207-219Subventions
Organisme : CIHR
ID : MOP-11-51-31
Pays : Canada
Organisme : CIHR
ID : RFN 152985
Pays : Canada
Organisme : CIHR
ID : 159815
Pays : Canada
Organisme : CIHR
ID : 162303
Pays : Canada
Informations de copyright
© 2021 Johan Gobom et al., published by De Gruyter, Berlin/Boston.
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