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

Abstract

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.

• Authors: Johan Gobom, Lucilla Parnetti, Pedro Rosa-Neto, Martin Vyhnalek, Serge Gauthier, Samuela Cataldi, Ondrej Lerch, Jan Laczo, Katerina Cechova, Marcus Clarin, Andrea L Benet, Tharick A Pascoal, Neserine Rahmouni, Manu Vandijck, Else Huyck, Nathalie Le Bastard, Jenna Stevenson, Mira Chamoun, Daniel Alcolea, Alberto Lleó, Ulf Andreasson, Marcel M Verbeek, Giovanni Bellomo, Roberta Rinaldi, Nicholas J Ashton, Henrik Zetterberg, Katerina Sheardova, Jakub Hort, Kaj Blennow
• Journal: Clinical chemistry and laboratory medicine (Clin Chem Lab Med) Vol. 60 Issue 2 Pg. 207-219 (01 27 2022) ISSN: 1437-4331 [Electronic] Germany
• PMID: 34773730 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2021 Johan Gobom et al., published by De Gruyter, Berlin/Boston.

Chemical References

• Amyloid beta-Peptides
• Biomarkers
• Peptide Fragments
• tau Proteins

Topics

• Alzheimer Disease (cerebrospinal fluid, diagnosis)
• Amyloid beta-Peptides (cerebrospinal fluid)
• Biomarkers (cerebrospinal fluid)
• Humans
• Immunoassay (methods)
• Peptide Fragments (cerebrospinal fluid)
• Reproducibility of Results
• tau Proteins (cerebrospinal fluid)