Validation of the LUMIPULSE automated immunoassay for the measurement of core AD biomarkers in cerebrospinal fluid

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 diagnosti...

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Detalles Bibliográficos
Autores: Gobom, J, Parnetti, L, Rosa-Neto, P, Vyhnalek, M, Gauthier, S, Cataldi, S, Lerch, O, Laczo, J, Cechova, K, Clarin, M, Benet, AI, Pascoal, TA, Rahmouni, N, Vandijck, M, Huyck, E, Le Bastard, N, Stevenson, J, Chamoun, M, Alcolea, D, Lleo, A, Andreasson, U, Verbeek, MM, Bellomo, G, Rinaldi, R, Ashton, N, Zetterberg, H, Sheardova, K, Hort, J, Blennow, K
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2022
País:España
Institución:Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau)
Repositorio:r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau
OAI Identifier:oai:iibsantpau.fundanetsuite.com:p6310
Acceso en línea:https://iibsantpau.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=6310
https://ddd.uab.cat/record/280914
Access Level:acceso abierto
Palabra clave:Alzheimer's disease
biomarkers
immunoassay
LUMIPULSE
validation
Descripción
Sumario: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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