J 2022

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

GOBOM, J., L. PARNETTI, P. ROSA-NETO, Martin VYHNALEK, S. GAUTHIER et. al.

Basic information

Original name

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

Authors

GOBOM, J. (guarantor), L. PARNETTI, P. ROSA-NETO, Martin VYHNALEK (203 Czech Republic), S. GAUTHIER, S. CATALDI, O. LERCH, J. LACZO, Katerina CECHOVA (203 Czech Republic), M. CLARIN, A. I. BENET, T. A. PASCOAL, N. RAHMOUNI, M. VANDIJCK, E. HUYCK, N. LE BASTARD, J. STEVENSON, M. CHAMOUN, D. ALCOLEA, A. LLEO, U. ANDREASSON, M. M. VERBEEK, G. BELLOMO, R. RINALDI, N. ASHTON, H. ZETTERBERG, Kateřina SHEARDOVÁ (203 Czech Republic, belonging to the institution), Jakub HORT (203 Czech Republic, belonging to the institution) and K. BLENNOW

Edition

Clinical Chemistry and Laboratory medicine, BERLIN, WALTER DE GRUYTER & CO, 2022, 1434-6621

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

20602 Medical laboratory technology ;

Country of publisher

Germany

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

Impact factor

Impact factor: 6.800

RIV identification code

RIV/00216224:14110/22:00125190

Organization unit

Faculty of Medicine

UT WoS

000737400000003

Keywords in English

Alzheimer's disease; biomarkers; immunoassay; LUMIPULSE; validation

Tags

Tags

International impact, Reviewed
Změněno: 1/2/2022 11:33, Mgr. Tereza Miškechová

Abstract

V originále

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.