Clinical and analytical comparison of six Simoa assays for plasma P-tau isoforms P-tau181, P-tau217, and P-tau231

Sherif Bayoumy; Inge M W Verberk; Ben den Dulk; Zulaiga Hussainali; Marissa Zwan; Wiesje M van der Flier; Nicholas J Ashton; Henrik Zetterberg; Kaj Blennow; Jeroen Vanbrabant; Erik Stoops; Eugeen Vanmechelen; Jeffrey L Dage; Charlotte E Teunissen

doi:10.1186/s13195-021-00939-9

Clinical and analytical comparison of six Simoa assays for plasma P-tau isoforms P-tau181, P-tau217, and P-tau231

Alzheimers Res Ther. 2021 Dec 4;13(1):198. doi: 10.1186/s13195-021-00939-9.

Authors

Sherif Bayoumy^#¹, Inge M W Verberk^#², Ben den Dulk², Zulaiga Hussainali², Marissa Zwan³, Wiesje M van der Flier^{3

4}, Nicholas J Ashton^{5

6

7

8}, Henrik Zetterberg^{5

9

10

11

12}, Kaj Blennow^{5

9}, Jeroen Vanbrabant¹³, Erik Stoops¹³, Eugeen Vanmechelen¹³, Jeffrey L Dage^{14

15}, Charlotte E Teunissen²

Affiliations

¹ Neurochemistry Laboratory, Department of Clinical Chemistry, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam UMC, Boelelaan 1117, Amsterdam, 1081 HV, The Netherlands. s.s.a.bayoumy@amsterdamumc.nl.
² Neurochemistry Laboratory, Department of Clinical Chemistry, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam UMC, Boelelaan 1117, Amsterdam, 1081 HV, The Netherlands.
³ Alzheimer Center, Department of Neurology, Vrije Universiteit Amsterdam, Amsterdam UMC, Amsterdam, The Netherlands.
⁴ Department of Epidemiology and Data Science, Vrije Universiteit Amsterdam, Amsterdam UMC, Amsterdam, The Netherlands.
⁵ Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.
⁶ Wallenberg Centre for Molecular and Translational Medicine, University of Gothenburg, Gothenburg, Sweden.
⁷ King's College London, Institute of Psychiatry, Psychology and Neuroscience, Maurice Wohl Institute Clinical Neuroscience Institute, London, UK.
⁸ NIHR Biomedical Research Centre for Mental Health and Biomedical Research Unit for Dementia at South London and Maudsley NHS Foundation, London, UK.
⁹ Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden.
¹⁰ Department of Neurodegenerative Disease, UCL Institute of Neurology, Queen Square, London, UK.
¹¹ UK Dementia Research Institute at UCL, London, UK.
¹² Hong Kong Center for Neurodegenerative Diseases, Hong Kong, China.
¹³ ADx NeuroSciences NV, Technologiepark 94, Gent, Belgium.
¹⁴ Eli Lilly and Company, Indianapolis, IN, 46285, USA.
¹⁵ Stark Neuroscience Research Institute, Indiana University School of Medicine, Indianapolis, IN, 46202, USA.

^# Contributed equally.

Abstract

Introduction: Studies using different assays and technologies showed highly promising diagnostic value of plasma phosphorylated (P-)tau levels for Alzheimer's disease (AD). We aimed to compare six P-tau Simoa assays, including three P-tau181 (Eli Lilly, ADx, Quanterix), one P-tau217 (Eli Lilly), and two P-tau231 (ADx, Gothenburg).

Methods: We studied the analytical (sensitivity, precision, parallelism, dilution linearity, and recovery) and clinical (40 AD dementia patients, age 66±8years, 50%F; 40 age- and sex-matched controls) performance of the assays.

Results: All assays showed robust analytical performance, and particularly P-tau217 Eli Lilly; P-tau231 Gothenburg and all P-tau181 assays showed robust clinical performance to differentiate AD from controls, with AUCs 0.936-0.995 (P-tau231 ADx: AUC = 0.719). Results obtained with all P-tau181 assays, P-tau217 Eli Lilly assay, and P-tau231 Gothenburg assay strongly correlated (Spearman's rho > 0.86), while correlations with P-tau231 ADx results were moderate (rho < 0.65).

Discussion: P-tau isoforms can be measured robustly by several novel high-sensitive Simoa assays.

Keywords: Alzheimer’s disease; Analytical validation; Blood biomarkers; Clinical validation; P-tau181; P-tau217; P-tau231; Phosphorylated tau proteins; Simoa; Ultra-sensitive immunoassays.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Aged
Alzheimer Disease* / diagnosis
Amyloid beta-Peptides
Biomarkers
Humans
Middle Aged
Phosphorylation
Protein Isoforms
tau Proteins* / metabolism

Substances

Amyloid beta-Peptides
Biomarkers
Protein Isoforms
tau Proteins

Grants and funding

R01 AG068398/AG/NIA NIH HHS/United States