Elecsys® Total-Tau and Phospho-Tau (181P) CSF assays: Analytical performance of the novel, fully automated immunoassays for quantification of tau proteins in human cerebrospinal fluid

Valeria Lifke; Gwendlyn Kollmorgen; Ekaterina Manuilova; Tobias Oelschlaegel; Lars Hillringhaus; Monika Widmann; Christine A F von Arnim; Markus Otto; Robert H Christenson; Jennifer L Powers; Leslie M Shaw; Oskar Hansson; James D Doecke; Qiao-Xin Li; Charlotte Teunissen; Hayrettin Tumani; Kaj Blennow

doi:10.1016/j.clinbiochem.2019.05.005

Elecsys^® Total-Tau and Phospho-Tau (181P) CSF assays: Analytical performance of the novel, fully automated immunoassays for quantification of tau proteins in human cerebrospinal fluid

Clin Biochem. 2019 Oct:72:30-38. doi: 10.1016/j.clinbiochem.2019.05.005. Epub 2019 May 23.

Authors

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

Affiliations

¹ Roche Diagnostics GmbH, Nonnenwald 2, 82377 Penzberg, Germany. Electronic address: [email protected].
² Roche Diagnostics GmbH, Nonnenwald 2, 82377 Penzberg, Germany. Electronic address: [email protected].
³ Roche Diagnostics GmbH, Nonnenwald 2, 82377 Penzberg, Germany. Electronic address: [email protected].
⁴ Roche Diagnostics GmbH, Nonnenwald 2, 82377 Penzberg, Germany. Electronic address: [email protected].
⁵ Roche Diagnostics GmbH, Nonnenwald 2, 82377 Penzberg, Germany. Electronic address: [email protected].
⁶ Amsterdam University Medical Center, Vrije Universiteit, De Boelelaan 1117, 1081 HV Amsterdam, Netherlands. Electronic address: [email protected].
⁷ Clinic for Neurology, University Clinic Ulm, Oberer Eselsberg 45, 89081 Ulm, Germany. Electronic address: [email protected].
⁸ Clinic for Neurology, University Clinic Ulm, Oberer Eselsberg 45, 89081 Ulm, Germany. Electronic address: [email protected].
⁹ Department of Pathology, University of Maryland School of Medicine, 655 W Baltimore S, Baltimore, MD 21201, USA. Electronic address: [email protected].
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: [email protected].
¹¹ Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, 3400 Civic Center Blvd, Philadelphia, PA 19104, USA. Electronic address: [email protected].
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: [email protected].
¹³ The Commonwealth Scientific and Industrial Research Organisation/Australian E-Health Research Centre, Butterfield St & Bowen Bridge Rd, Herston, QLD 4029, Australia. Electronic address: [email protected].
¹⁴ The Florey Institute of Neuroscience and Mental Health, University of Melbourne, 30 Royal Parade, Parkville, VIC 3052, Australia. Electronic address: [email protected].
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: [email protected].
¹⁶ Clinic for Neurology, University Clinic Ulm, Oberer Eselsberg 45, 89081 Ulm, Germany. Electronic address: [email protected].
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: [email protected].

PMID: 31129184
DOI: 10.1016/j.clinbiochem.2019.05.005

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.

Keywords: Alzheimer's disease; Biomarkers; CSF; Fully automated immunoassay; Phosphorylated tau; Total tau.

Publication types

Multicenter Study

MeSH terms

Alzheimer Disease / cerebrospinal fluid
Alzheimer Disease / diagnosis
Biomarkers / cerebrospinal fluid
Biomarkers / chemistry
Humans
Immunoassay / methods*
Limit of Detection
Phosphorylation
Reproducibility of Results
tau Proteins / cerebrospinal fluid*
tau Proteins / chemistry

Substances

Biomarkers
tau Proteins