Evidence map›Paper›PMID 33169916›Full record

ArticleEMBO molecular medicine2020

Novel tau biomarkers phosphorylated at T181, T217 or T231 rise in the initial stages of the preclinical Alzheimer's continuum when only subtle changes in Aβ pathology are detected.

Marc Suárez-Calvet, Thomas K Karikari, Nicholas J Ashton, Juan Lantero Rodríguez, Marta Milà-Alomà, Juan Domingo Gispert, Gemma Salvadó, Carolina Minguillon, Karine Fauria, Mahnaz Shekari and 12 more

Registry-linked trialOpen access · goldAbstract read
In one paragraph

Article in EMBO molecular medicine, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT06246019 (The Clinical Impact of the Novel Alzheimer's Blood-based Biomarkers), which is not on this map. Cited by 249 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
249citing papers in PubMed, 2 pooled it
23.7field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT06246019 unknown statusnot on this mapstarted 2024, after this paper: background citation

The Clinical Impact of the Novel Alzheimer's Blood-based Biomarkers: the PLASMAR Study

Typeobservational_patient_registrySponsorHospital del Mar Research Institute (IMIM)Ran2024 to 2025Enrolled200ConditionsAlzheimer Disease, Cognitive Impairment, Dementia, Neurodegenerative DiseasesArmsEarly adoption of blood-based biomarkers for Alzheimer's disease
3 · Its place in the literature

Who cites it

249 citing papers in PubMed, 2 syntheses or guidelines pooled it, 399 citations in OpenAlex.

  1. Pooled it
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  13. Associations ofAlzheimer's & dementia : the journal of the Alzheimer's Association · 2026
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  14. Observational
  15. Review
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  19. Association of plasma p-tau and p-tau/Aβ ratio with Alzheimer's pathology.The journal of prevention of Alzheimer's disease · 2026
    Article
  20. Article

189 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

22 authors at 7 institutions in 5 countries.

Marc Suárez-CalvetBarcelonaβeta Brain Research Center (BBRC), Pasqual Maragall Foundation, Barcelona, Spain.ORCID 0000-0002-2993-569X
Thomas K KarikariDepartment of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
Nicholas J AshtonDepartment of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.ORCID 0000-0002-6353-9316
Juan Lantero RodríguezDepartment of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
Marta Milà-AlomàBarcelonaβeta Brain Research Center (BBRC), Pasqual Maragall Foundation, Barcelona, Spain.
Juan Domingo GispertBarcelonaβeta Brain Research Center (BBRC), Pasqual Maragall Foundation, Barcelona, Spain.
Gemma SalvadóBarcelonaβeta Brain Research Center (BBRC), Pasqual Maragall Foundation, Barcelona, Spain.
Carolina MinguillonBarcelonaβeta Brain Research Center (BBRC), Pasqual Maragall Foundation, Barcelona, Spain.
Karine FauriaBarcelonaβeta Brain Research Center (BBRC), Pasqual Maragall Foundation, Barcelona, Spain.
Mahnaz ShekariBarcelonaβeta Brain Research Center (BBRC), Pasqual Maragall Foundation, Barcelona, Spain.
Oriol Grau-RiveraBarcelonaβeta Brain Research Center (BBRC), Pasqual Maragall Foundation, Barcelona, Spain.
Eider M Arenaza-UrquijoBarcelonaβeta Brain Research Center (BBRC), Pasqual Maragall Foundation, Barcelona, Spain.
Aleix Sala-VilaBarcelonaβeta Brain Research Center (BBRC), Pasqual Maragall Foundation, Barcelona, Spain.
Gonzalo Sánchez-BenavidesBarcelonaβeta Brain Research Center (BBRC), Pasqual Maragall Foundation, Barcelona, Spain.
José Maria González-de-EchávarriBarcelonaβeta Brain Research Center (BBRC), Pasqual Maragall Foundation, Barcelona, Spain.
Gwendlyn KollmorgenRoche Diagnostics GmbH, Penzberg, Germany.
Erik StoopsADx NeuroSciences, Ghent, Belgium.
Eugeen VanmechelenADx NeuroSciences, Ghent, Belgium.
Henrik ZetterbergDepartment of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
Kaj BlennowDepartment of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.ORCID 0000-0002-1890-4193
José Luis MolinuevoBarcelonaβeta Brain Research Center (BBRC), Pasqual Maragall Foundation, Barcelona, Spain.ORCID 0000-0003-0485-6001
ALFA Study
Pasqual Maragall Foundation · ESUniversitat Pompeu Fabra · ESADx NeuroSciences · BESahlgrenska University Hospital · SEUniversity of Gothenburg · SEKing's College London · GBRoche Pharma AG (Germany) · DE

Funding

ALF-agreement ALFGBG-715986Alzheimer's Association (AA) TriBEKa-17-519007Alzheimer's Drug Discovery Foundation (ADDF) 201809-2016862Alzheimer's Drug Discovery Foundation (ADDF) RDAPB-201809-2016615BrightFocus Foundation (BFF) A2020812FCatalan Government 2017-SGR-892EC | H2020 | H2020 Priority Excellent Science | H2020 European Research Council (ERC) 681712EC | H2020 | H2020 Priority Excellent Science | H2020 Marie Skłodowska-Curie Actions (MSCA) 752310EU Joint Programme - Neurodegenerative Disease Research (JPND) JPND2019-466-236Hjärnfonden Sweden FO2017-0243"la Caixa" Foundation ("la Caixa") LCF/PR/GN17/50300004MEC | Instituto de Salud Carlos III (ISCIII) CP II 17/00029MEC | Instituto de Salud Carlos III (ISCIII) PI19/00155Ministerio de Ciencia, Innovación y Universidades (MCIU) FJCI-2017-33437Ministerio de Ciencia, Innovación y Universidades (MCIU) IJC2018-037478-IMinisterio de Ciencia, Innovación y Universidades (MCIU) RYC2018-026053-IMinisterio de Economía y Competitividad (MEC) IEDI-2016-00690Ministerio de Economía y Competitividad (MEC) RYC-2013-13054Svenska Forskningsrådet Formas 2017-00915Svenska Forskningsrådet Formas 2018-02532Swedish Alzheimer Foundation AF-742881Swedish Alzheimer Foundation AF-930627Swedish State Support for Clinical Research ALFGBG-720931
6 · The paper itself

Abstract

In Alzheimer's disease (AD), tau phosphorylation in the brain and its subsequent release into cerebrospinal fluid (CSF) and blood is a dynamic process that changes during disease evolution. The main aim of our study was to characterize the pattern of changes in phosphorylated tau (p-tau) in the preclinical stage of the Alzheimer's continuum. We measured three novel CSF p-tau biomarkers, phosphorylated at threonine-181 and threonine-217 with an N-terminal partner antibody and at threonine-231 with a mid-region partner antibody. These were compared with an automated mid-region p-tau181 assay (Elecsys) as the gold standard p-tau measure. We demonstrate that these novel p-tau biomarkers increase more prominently in preclinical Alzheimer, when only subtle changes of amyloid-β (Aβ) pathology are detected, and can accurately differentiate Aβ-positive from Aβ-negative cognitively unimpaired individuals. Moreover, we show that the novel plasma N-terminal p-tau181 biomarker is mildly but significantly increased in the preclinical stage. Our results support the idea that early changes in neuronal tau metabolism in preclinical Alzheimer, likely in response to Aβ exposure, can be detected with these novel p-tau assays.

Indexed as

Prodromal SymptomsAgedAlzheimer DiseaseAmyloid beta-PeptidesBiomarkersBrainFemaleHumansLongitudinal StudiesMaleMiddle AgedPhosphorylationtau ProteinsAmyloid beta-PeptidesBiomarkerstau ProteinsAlzheimer’s diseasebiomarkercerebrospinal fluidplasmatau

Identifiers

PMID33169916
PMCPMC7721364
OpenAlexW3099667207

What OpenQuestion holds

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LicenceCC BY
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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.