Validation of the LUMIPULSE automated immunoassay for the measurement of core AD biomarkers in cerebrospinal fluid
Por:
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
Publicada:
27 ene 2022
Ahead of Print:
1 nov 2021
Resumen:
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.
Filiaciones:
Gobom, J:
Univ Gothenburg, Sahlgrenska Acad, Inst Neurosci & Physiol, Dept Psychiat & Neurochem, Gothenburg, Sweden
Sahlgrens Univ Hosp, Clin Neurochem Lab, Molndal, Sweden
Parnetti, L:
Univ Perugia, Sect Neurol, Lab Clin Neurochem, Perugia, Italy
Rosa-Neto, P:
McGill Univ, Dept Neurol & Neurosurg, Res Ctr Studies Aging,Psychiat & Pharmacol & Ther, Douglas Res Inst,Ctr Integre Univ Sante & Serv So, Montreal, PQ, Canada
Montreal Neurol Inst, Montreal, PQ, Canada
Vyhnalek, M:
Charles Univ Prague, Med Fac 2, Dept Neurol, Prague, Czech Republic
Motol Univ Hosp, Prague, Czech Republic
St Annes Univ Hosp, Int Clin Res Ctr, Brno, Czech Republic
Gauthier, S:
McGill Univ, Dept Neurol & Neurosurg, Res Ctr Studies Aging,Psychiat & Pharmacol & Ther, Douglas Res Inst,Ctr Integre Univ Sante & Serv So, Montreal, PQ, Canada
Montreal Neurol Inst, Montreal, PQ, Canada
Cataldi, S:
Univ Perugia, Sect Neurol, Lab Clin Neurochem, Perugia, Italy
Lerch, O:
Charles Univ Prague, Med Fac 2, Dept Neurol, Prague, Czech Republic
Motol Univ Hosp, Prague, Czech Republic
St Annes Univ Hosp, Int Clin Res Ctr, Brno, Czech Republic
Laczo, J:
Charles Univ Prague, Med Fac 2, Dept Neurol, Prague, Czech Republic
Motol Univ Hosp, Prague, Czech Republic
St Annes Univ Hosp, Int Clin Res Ctr, Brno, Czech Republic
Cechova, K:
Charles Univ Prague, Med Fac 2, Dept Neurol, Prague, Czech Republic
Motol Univ Hosp, Prague, Czech Republic
St Annes Univ Hosp, Int Clin Res Ctr, Brno, Czech Republic
Clarin, M:
Univ Gothenburg, Sahlgrenska Acad, Inst Neurosci & Physiol, Dept Psychiat & Neurochem, Gothenburg, Sweden
Sahlgrens Univ Hosp, Clin Neurochem Lab, Molndal, Sweden
Benet, AI:
Univ Gothenburg, Sahlgrenska Acad, Inst Neurosci & Physiol, Dept Psychiat & Neurochem, Gothenburg, Sweden
McGill Univ, McGill Ctr Studies Aging, Translat Neuroimaging Lab, Montreal, PQ, Canada
Pascoal, TA:
McGill Univ, McGill Ctr Studies Aging, Translat Neuroimaging Lab, Montreal, PQ, Canada
Rahmouni, N:
McGill Univ, McGill Ctr Studies Aging, Translat Neuroimaging Lab, Montreal, PQ, Canada
Vandijck, M:
Fujirebio Europe NV, Ghent, Belgium
Huyck, E:
Fujirebio Europe NV, Ghent, Belgium
Le Bastard, N:
Fujirebio Europe NV, Ghent, Belgium
Stevenson, J:
McGill Univ, McGill Ctr Studies Aging, Translat Neuroimaging Lab, Montreal, PQ, Canada
Chamoun, M:
McGill Univ, McGill Ctr Studies Aging, Translat Neuroimaging Lab, Montreal, PQ, Canada
Alcolea, D:
Univ Autonoma Barcelona, Dept Neurol, Memory Unit, Biomed Res Inst St Pau,Hosp Santa Creu & St Pau, Barcelona, Spain
Ctr Invest Biomed Red Enfermedades Neurodegenerat, Madrid, Spain
Lleo, A:
Univ Autonoma Barcelona, Dept Neurol, Memory Unit, Biomed Res Inst St Pau,Hosp Santa Creu & St Pau, Barcelona, Spain
Ctr Invest Biomed Red Enfermedades Neurodegenerat, Madrid, Spain
Andreasson, U:
Univ Gothenburg, Sahlgrenska Acad, Inst Neurosci & Physiol, Dept Psychiat & Neurochem, Gothenburg, Sweden
Sahlgrens Univ Hosp, Clin Neurochem Lab, Molndal, Sweden
Verbeek, MM:
Radboud Univ Nijmegen, Dept Lab Med, Med Ctr, Nijmegen, Netherlands
Radboud Univ Nijmegen, Radboud Alzheimer Ctr, Donders Inst Brain, Dept Neurol,Med Ctr, Nijmegen, Netherlands
Bellomo, G:
Univ Perugia, Sect Neurol, Lab Clin Neurochem, Perugia, Italy
Rinaldi, R:
Univ Perugia, Sect Neurol, Lab Clin Neurochem, Perugia, Italy
Ashton, N:
Univ Gothenburg, Sahlgrenska Acad, Inst Neurosci & Physiol, Dept Psychiat & Neurochem, Gothenburg, Sweden
Univ Gothenburg, Wallenberg Ctr Mol & Translat Med, Gothenburg, Sweden
Kings Coll London, Inst Psychiat, Maurice Wohl Clin Neurosci Inst, London, England
South London & Maudsley NHS Fdn, NIHR Biomed Res Ctr Mental Hlth, London, England
South London & Maudsley NHS Fdn, Biomed Res Unit Dementia, London, England
Zetterberg, H:
Univ Gothenburg, Sahlgrenska Acad, Inst Neurosci & Physiol, Dept Psychiat & Neurochem, Gothenburg, Sweden
Sahlgrens Univ Hosp, Clin Neurochem Lab, Molndal, Sweden
UCL Inst Neurol, Dept Neurodegenerat Dis, London, England
UK Dementia Res Inst UCL, London, England
Sheardova, K:
Charles Univ Prague, Med Fac 2, Dept Neurol, Prague, Czech Republic
Masaryk Univ, Dept Neurol 1, Fac Med, Brno, Czech Republic
St Annes Univ Hosp, Brno, Czech Republic
Hort, J:
Charles Univ Prague, Med Fac 2, Dept Neurol, Prague, Czech Republic
Motol Univ Hosp, Prague, Czech Republic
Masaryk Univ, Dept Neurol 1, Fac Med, Brno, Czech Republic
St Annes Univ Hosp, Brno, Czech Republic
Blennow, K:
Univ Gothenburg, Sahlgrenska Acad, Inst Neurosci & Physiol, Dept Psychiat & Neurochem, Gothenburg, Sweden
Sahlgrens Univ Hosp, Clin Neurochem Lab, Molndal, Sweden
hybrid, Green Published, All Open Access, Hybrid Gold, Green
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