Valeria Lifke1, Gwendlyn Kollmorgen2, Ekaterina Manuilova3, Tobias Oelschlaegel4, Lars Hillringhaus5, Monika Widmann6, Christine A F von Arnim7, Markus Otto8, Robert H Christenson9, Jennifer L Powers10, Leslie M Shaw11, Oskar Hansson12, James D Doecke13, Qiao-Xin Li14, Charlotte Teunissen15, Hayrettin Tumani16, Kaj Blennow17. 1. Roche Diagnostics GmbH, Nonnenwald 2, 82377 Penzberg, Germany. Electronic address: valeria.lifke@roche.com. 2. Roche Diagnostics GmbH, Nonnenwald 2, 82377 Penzberg, Germany. Electronic address: gwendlyn.kollmorgen@roche.com. 3. Roche Diagnostics GmbH, Nonnenwald 2, 82377 Penzberg, Germany. Electronic address: ekaterina.manuilova@roche.com. 4. Roche Diagnostics GmbH, Nonnenwald 2, 82377 Penzberg, Germany. Electronic address: tobias.oelschlaegel@roche.com. 5. Roche Diagnostics GmbH, Nonnenwald 2, 82377 Penzberg, Germany. Electronic address: lars.hillringhaus@roche.com. 6. Amsterdam University Medical Center, Vrije Universiteit, De Boelelaan 1117, 1081 HV Amsterdam, Netherlands. Electronic address: monika.widmann@roche.com. 7. Clinic for Neurology, University Clinic Ulm, Oberer Eselsberg 45, 89081 Ulm, Germany. Electronic address: christine.arnim@uni-ulm.de. 8. Clinic for Neurology, University Clinic Ulm, Oberer Eselsberg 45, 89081 Ulm, Germany. Electronic address: markus.otto@uni-ulm.de. 9. Department of Pathology, University of Maryland School of Medicine, 655 W Baltimore S, Baltimore, MD 21201, USA. Electronic address: rchristenson@umm.edu. 10. Division of Endocrinology, Metabolism and Lipid Research, School of Medicine, Washington University in St Louis, 660 S Euclid Ave, St. Louis, MO 63110, USA. Electronic address: powers.jennifer.l@wustl.edu. 11. Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, 3400 Civic Center Blvd, Philadelphia, PA 19104, USA. Electronic address: Leslie.Shaw2@uphs.upenn.edu. 12. Clinical Memory Research Unit, Lund University, VO Minnessjukdomar, Simrisbanv 14/4, 212 24 Malmö, Sweden; Memory Clinic, Skåne University Hospital, Inga Marie Nilssons gata 47, 214 21 Malmö, Sweden. Electronic address: oskar.hansson@med.lu.se. 13. The Commonwealth Scientific and Industrial Research Organisation/Australian E-Health Research Centre, Butterfield St & Bowen Bridge Rd, Herston, QLD 4029, Australia. Electronic address: James.Doecke@csiro.au. 14. The Florey Institute of Neuroscience and Mental Health, University of Melbourne, 30 Royal Parade, Parkville, VIC 3052, Australia. Electronic address: q.li@unimelb.edu.au. 15. Neurochemistry Laboratory and Biobank, Department of Clinical Chemistry, Amsterdam University Medical Center, Vrije Universiteit, De Boelelaan 1117, 1081, HV Amsterdam, the Netherlands. Electronic address: c.teunissen@vumc.nl. 16. Clinic for Neurology, University Clinic Ulm, Oberer Eselsberg 45, 89081 Ulm, Germany. Electronic address: hayrettin.tumani@uni-ulm.de. 17. Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Göteborgsvägen 31, 431 80 Mölndal, Sweden; Institute of Neuroscience and Physiology, Dept. of Psychiatry and Neurochemistry, The Sahlgrenska Academy at University of Gothenburg, Wallinsgatan 6, 431 41 Mölndal, Sweden. Electronic address: kaj.blennow@neuro.gu.se.
Abstract
BACKGROUND: Total tau (tTau) and phosphorylated 181P tau (pTau) are supportive diagnostic cerebrospinal fluid (CSF) biomarkers for Alzheimer's disease. Manual CSF tau assays are limited by lot-to-lot and between-laboratory variability and long incubation/turnaround times. Elecsys® Total-Tau CSF and Phospho-Tau (181P) CSF immunoassays were developed for fully automated cobas e analyzers, allowing broader access in clinical practice and trials. METHODS: Analytical performance, reproducibility, method comparisons with commercially available assays, and lot-to-lot and platform comparability (cobas e 601/411) of the Elecsys® CSF assays were assessed. Tau distributions and concentration ranges were evaluated in CSF samples from two clinical cohorts. RESULTS: Both assays showed high sensitivity (limit of quantitation [LoQ]: 63 pg/mL [tTau]; 4 pg/mL [pTau]) and linearity over the measuring range (80-1300 pg/mL; 8-120 pg/mL), which covered the entire concentration range measured in clinical samples. Lot-to-lot and platform comparability demonstrated good consistency (Pearson's r: 0.998; 1.000). Multicenter evaluation coefficients of variation (CVs): repeatability, < 1.8%; intermediate precision, < 2.8%; between-laboratory variability, < 2.7% (both assays); and total reproducibility, < 6.7% (tTau) and < 4.7% (pTau). Elecsys® CSF assays demonstrated good correlation with commercially available tau assays. CONCLUSIONS: Elecsys® Total-Tau CSF and Phospho-Tau (181P) CSF assays demonstrate good analytical performance with clinically relevant measuring ranges; data support their use in clinical trials and practice.
BACKGROUND: Total tau (tTau) and phosphorylated 181P tau (pTau) are supportive diagnostic cerebrospinal fluid (CSF) biomarkers for Alzheimer's disease. Manual CSF tau assays are limited by lot-to-lot and between-laboratory variability and long incubation/turnaround times. Elecsys® Total-Tau CSF and Phospho-Tau (181P) CSF immunoassays were developed for fully automated cobas e analyzers, allowing broader access in clinical practice and trials. METHODS: Analytical performance, reproducibility, method comparisons with commercially available assays, and lot-to-lot and platform comparability (cobas e 601/411) of the Elecsys® CSF assays were assessed. Tau distributions and concentration ranges were evaluated in CSF samples from two clinical cohorts. RESULTS: Both assays showed high sensitivity (limit of quantitation [LoQ]: 63 pg/mL [tTau]; 4 pg/mL [pTau]) and linearity over the measuring range (80-1300 pg/mL; 8-120 pg/mL), which covered the entire concentration range measured in clinical samples. Lot-to-lot and platform comparability demonstrated good consistency (Pearson's r: 0.998; 1.000). Multicenter evaluation coefficients of variation (CVs): repeatability, < 1.8%; intermediate precision, < 2.8%; between-laboratory variability, < 2.7% (both assays); and total reproducibility, < 6.7% (tTau) and < 4.7% (pTau). Elecsys® CSF assays demonstrated good correlation with commercially available tau assays. CONCLUSIONS: Elecsys® Total-Tau CSF and Phospho-Tau (181P) CSF assays demonstrate good analytical performance with clinically relevant measuring ranges; data support their use in clinical trials and practice.
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