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.
| Original language | English |
|---|---|
| Article number | 198 |
| Journal | Alzheimer's Research and Therapy |
| Volume | 13 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - 1 Dec 2021 |
Keywords
- Alzheimer’s disease
- Analytical validation
- Blood biomarkers
- Clinical validation
- P-tau181
- P-tau217
- P-tau231
- Phosphorylated tau proteins
- Simoa
- Ultra-sensitive immunoassays
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In: Alzheimer's Research and Therapy, Vol. 13, No. 1, 198, 01.12.2021.
Research output: Contribution to journal › Article › Academic › peer-review
TY - JOUR
T1 - Clinical and analytical comparison of six Simoa assays for plasma P-tau isoforms P-tau181, P-tau217, and P-tau231
AU - Bayoumy, Sherif
AU - Verberk, Inge M. W.
AU - den Dulk, Ben
AU - Hussainali, Zulaiga
AU - Zwan, Marissa
AU - van der Flier, Wiesje M.
AU - Ashton, Nicholas J.
AU - Zetterberg, Henrik
AU - Blennow, Kaj
AU - Vanbrabant, Jeroen
AU - Stoops, Erik
AU - Vanmechelen, Eugeen
AU - Dage, Jeffrey L.
AU - Teunissen, Charlotte E.
N1 - Funding Information: Research of the Neurochemistry lab and Alzheimer center Amsterdam is part of the neurodegeneration research program of Amsterdam Neuroscience. Recruitment was partly accomplished through the Dutch Brain Research Registry (Hersenonderzoek.nl) that facilitates participant recruitment for neuroscience studies ( www.hersenonderzoek.nl ). Hersenonderzoek.nl is funded by ZonMw-Memorabel (project no 73305095003), a project in the context of the Dutch Deltaplan Dementie, Gieskes-Strijbis Foundation, the Alzheimer’s Society in the Netherlands and Brain Foundation Netherlands. Funding Information: IV is appointed on a research grant by Alzheimer Nederland (NL-17004). HZ is a Wallenberg Scholar supported by grants from the Swedish Research Council (#2018-02532); the European Research Council (#681712); Swedish State Support for Clinical Research (#ALFGBG-720931); the Alzheimer Drug Discovery Foundation (ADDF), USA (#201809-2016862); the AD Strategic Fund and the Alzheimer’s Association (#ADSF-21-831376-C, #ADSF-21-831381-C, and #ADSF-21-831377-C); the Olav Thon Foundation, the Erling-Persson Family Foundation, Stiftelsen för Gamla Tjänarinnor, Hjärnfonden, Sweden (#FO2019-0228); the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No 860197 (MIRIADE); and the UK Dementia Research Institute at UCL. KB is supported by the Swedish Research Council (#2017-00915); the Alzheimer Drug Discovery Foundation (ADDF), USA (#RDAPB-201809-2016615); the Swedish Alzheimer Foundation (#AF-742881), Hjärnfonden, Sweden (#FO2017-0243); the Swedish state under the agreement between the Swedish government and the County Councils; the ALF-agreement (#ALFGBG-715986); the European Union Joint Program for Neurodegenerative Disorders (JPND2019-466-236); and the National Institute of Health (NIH) USA (grant #1R01AG068398-01). Research of CT is supported by the European Commission (Marie Curie International Training Network, grant agreement No 860197 (MIRIADE), and JPND), Health Holland, the Dutch Research Council (ZonMW), Alzheimer Drug Discovery Foundation, The Selfridges Group Foundation, Alzheimer Netherlands, and Alzheimer Association. CT and WF are recipients of ABOARD, which is a public-private partnership receiving funding from ZonMW (#73305095007) and Health~Holland, Topsector Life Sciences & Health (PPP-allowance; #LSHM20106). More than 30 partners participate in ABOARD. ABOARD also receives funding from Edwin Bouw Fonds and Gieskes-Strijbisfonds. The chair of Wiesje van der Flier is supported by the Pasman stichting. Alzheimer Center Amsterdam is supported by Stichting Alzheimer Nederland and Stichting VUmc fonds. Funding Information: SB, IV, BDD, ZH, MZ, and NA report no conflicts of interest. WF holds the Pasman chair. WF has performed contract research for Biogen MA Inc. and Boehringer Ingelheim. WF has been an invited speaker at Boehringer Ingelheim, Biogen MA Inc., Danone, Eisai, WebMD Neurology (Medscape). WF is a consultant to Oxford Health Policy Forum CIC, Roche, and Biogen MA Inc. WF participated in an advisory board of Biogen MA Inc. WF is associate editor at Alzheimer’s, Research & Therapy. All funding is paid to her institution. HZ has served at scientific advisory boards and/or as a consultant for Abbvie, Alector, Annexon, AZTherapies, CogRx, Denali, Eisai, Nervgen, Pinteon Therapeutics, Red Abbey Labs, Roche, Samumed, Siemens Healthineers, Triplet Therapeutics, and Wave; has given lectures in symposia sponsored by Cellectricon, Fujirebio, Alzecure and Biogen; and is a co-founder of Brain Biomarker Solutions in Gothenburg AB (BBS), which is a part of the GU Ventures Incubator Program. KB has served as a consultant or at advisory boards for Abcam, Axon, Biogen, JOMDD/Shimadzu, Lilly, MagQu, Prothena, Roche Diagnostics and Siemens Healthineers, and as data monitoring committee for Julius Clinical and Novartis. All payment was made to him personally. KB is a co-founder of Brain Biomarker Solutions in Gothenburg AB (BBS), which is a part of the GU Ventures Incubator Program. JV and ES are employees of ADx NeuroSciences. EV is co-founder of ADx NeuroSciences. JD a minor stock holder of Eli Lilly and Company and inventor on the patent application used in the Lilly P-tau217 assay. CT has a collaboration contract with ADx Neurosciences and Quanterix and performed contract research or received grants from AC-Immune, Axon Neurosciences, Biogen, Brainstorm Therapeutics, Celgene, EIP Pharma, Eisai, PeopleBio, Roche, Toyama, Vivoryon. CT serves on editorial boards of Medidact Neurologi/Springer, Alzheimer Research and Therapy, Neurology: Neuroimmunology & Neuroinflammation, and is an editor of a Neuromethods book Springer. WF: Research programs of WF have been funded by ZonMW, NWO, EU-FP7, EU-JPND, Alzheimer Nederland, CardioVascular Onderzoek Nederland, Health~Holland, Topsector Life Sciences & Health, stichting Dioraphte, Gieskes-Strijbis fonds, stichting Equilibrio, Pasman stichting, Biogen MA Inc., Boehringer Ingelheim, Life-MI, AVID, Roche NL, Biogen NL, Novartis NL, Philips, Neurocast, Fujifilm, Combinostics. Funding Information: Research of the Neurochemistry lab and Alzheimer center Amsterdam is part of the neurodegeneration research program of Amsterdam Neuroscience. Recruitment was partly accomplished through the Dutch Brain Research Registry (Hersenonderzoek.nl) that facilitates participant recruitment for neuroscience studies (www.hersenonderzoek.nl ). Hersenonderzoek.nl is funded by ZonMw-Memorabel (project no 73305095003), a project in the context of the Dutch Deltaplan Dementie, Gieskes-Strijbis Foundation, the Alzheimer?s Society in the Netherlands and Brain Foundation Netherlands. Publisher Copyright: © 2021, The Author(s).
PY - 2021/12/1
Y1 - 2021/12/1
N2 - 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.
AB - 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.
KW - Alzheimer’s disease
KW - Analytical validation
KW - Blood biomarkers
KW - Clinical validation
KW - P-tau181
KW - P-tau217
KW - P-tau231
KW - Phosphorylated tau proteins
KW - Simoa
KW - Ultra-sensitive immunoassays
UR - http://www.scopus.com/inward/record.url?scp=85120730955&partnerID=8YFLogxK
U2 - https://doi.org/10.1186/s13195-021-00939-9
DO - https://doi.org/10.1186/s13195-021-00939-9
M3 - Article
C2 - 34863295
SN - 1758-9193
VL - 13
JO - Alzheimer's Research and Therapy
JF - Alzheimer's Research and Therapy
IS - 1
M1 - 198
ER -