Evidence map›Paper›PMID 40551285›Full record

ArticleAlzheimer's & dementia : the journal of the Alzheimer's Association2025

Diagnostic performance of plasma Aβ42/40 ratio, p-tau181, GFAP, and NfL along the continuum of Alzheimer's disease and non-AD dementias: An international multi-center study.

James D Doecke, Giovanni Bellomo, Lisa Vermunt, Daniel Alcolea, Steffen Halbgebauer, Sjors In 't Veld, Niklas Mattsson-Carlgren, Katerina Veverova, Christopher J Fowler, Lynn Boonkamp and 26 more

Abstract readMulticenter Study
In one paragraph

Article in Alzheimer's & dementia : the journal of the Alzheimer's Association, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed, 1 pooled it
–field-weighted citation impact
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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

20 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Dulaglutide and neurodegeneration biomarkers: REWIND post hoc analysis.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026
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  8. Precision medicine for Alzheimer's disease in Down syndrome.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026
    Article
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  11. Article
  12. Review
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  14. Review
  15. Circulating neurodegenerative brain injury markers and hip fracture and fall hospitalizations: the Cardiovascular Health Study.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2025
    Article
  16. Review
  17. Brain and retina in Alzheimer's disease: Pathological intersections and estimates from imaging.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025
    Review
  18. Article
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  20. Article
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

36 authors.

James D DoeckeAustralian E-Health Research Centre, CSIRO, Herston, Queensland, Australia.ORCID 0000-0003-2863-0293
Giovanni BellomoSection of Neurology, Laboratory of Clinical Neurochemistry, Department of Medicine and Surgery, University of Perugia, Perugia, Italy.
Lisa VermuntNeurochemistry Laboratory, Department of Laboratory Medicine, Amsterdam Neuroscience, Amsterdam University Medical Center, Vrije Universiteit, Amsterdam, the Netherlands.
Daniel AlcoleaDepartment of Neurology, Institut d'Investigacions Biomèdiques Sant Pau - Hospital de Sant Pau, Universitat Autònoma de Barcelona, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
Steffen HalbgebauerDepartment of Neurology, University of Ulm, Ulm, Germany.
Sjors In 't VeldNeurochemistry Laboratory, Department of Laboratory Medicine, Amsterdam Neuroscience, Amsterdam University Medical Center, Vrije Universiteit, Amsterdam, the Netherlands.
Niklas Mattsson-CarlgrenClinical Memory Research Unit, Department of Clinical Sciences Malmö, Faculty of Medicine, Lund University, Lund, Sweden.
Katerina VeverovaMemory Clinic, Department of Neurology, Charles University, Second Faculty of Medicine and Motol University Hospital, Prague, Czech Republic.
Christopher J FowlerThe University of Melbourne, The Florey Institute, Victoria, Melbourne, Australia.
Lynn BoonkampNeurochemistry Laboratory, Department of Laboratory Medicine, Amsterdam Neuroscience, Amsterdam University Medical Center, Vrije Universiteit, Amsterdam, the Netherlands.
Isabel M HoutkampNeurochemistry Laboratory, Department of Laboratory Medicine, Amsterdam Neuroscience, Amsterdam University Medical Center, Vrije Universiteit, Amsterdam, the Netherlands.
Marleen Koel-SimmerlinkNeurochemistry Laboratory, Department of Laboratory Medicine, Amsterdam Neuroscience, Amsterdam University Medical Center, Vrije Universiteit, Amsterdam, the Netherlands.
Inge M W VerberkNeurochemistry Laboratory, Department of Laboratory Medicine, Amsterdam Neuroscience, Amsterdam University Medical Center, Vrije Universiteit, Amsterdam, the Netherlands.
Lorenzo GaetaniSection of Neurology, Laboratory of Clinical Neurochemistry, Department of Medicine and Surgery, University of Perugia, Perugia, Italy.
Andrea TojaSection of Neurology, Laboratory of Clinical Neurochemistry, Department of Medicine and Surgery, University of Perugia, Perugia, Italy.
Anna Lidia WojdałaNeurochemistry Laboratory, Department of Laboratory Medicine, Amsterdam Neuroscience, Amsterdam University Medical Center, Vrije Universiteit, Amsterdam, the Netherlands.
Juan ForteaDepartment of Neurology, Institut d'Investigacions Biomèdiques Sant Pau - Hospital de Sant Pau, Universitat Autònoma de Barcelona, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
Yolande PijnenburgAlzheimer Center Amsterdam, Department of Neurology, Amsterdam Neuroscience, Amsterdam University Medical Centers, Amsterdam, the Netherlands.
Afina LemstraAlzheimer Center Amsterdam, Department of Neurology, Amsterdam Neuroscience, Amsterdam University Medical Centers, Amsterdam, the Netherlands.
Wiesje van der FlierAlzheimer Center Amsterdam, Department of Neurology, Amsterdam Neuroscience, Amsterdam University Medical Centers, Amsterdam, the Netherlands.
Jakub HortMemory Clinic, Department of Neurology, Charles University, Second Faculty of Medicine and Motol University Hospital, Prague, Czech Republic.
Markus OttoDepartment of Neurology, University of Ulm, Ulm, Germany.
Oskar HanssonClinical Memory Research Unit, Department of Clinical Sciences Malmö, Faculty of Medicine, Lund University, Lund, Sweden.
Lucilla ParnettiSection of Neurology, Laboratory of Clinical Neurochemistry, Department of Medicine and Surgery, University of Perugia, Perugia, Italy.
Colin L MastersThe University of Melbourne, The Florey Institute, Victoria, Melbourne, Australia.
Alberto LleóDepartment of Neurology, Institut d'Investigacions Biomèdiques Sant Pau - Hospital de Sant Pau, Universitat Autònoma de Barcelona, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
Armand González-EscalanteBarcelonaβeta Brain Research Center (BBRC), Pasqual Maragall Foundation, Sant Martí, Barcelona, Spain.
José ContadorBarcelonaβeta Brain Research Center (BBRC), Pasqual Maragall Foundation, Sant Martí, Barcelona, Spain.
Marc Suárez-CalvetBarcelonaβeta Brain Research Center (BBRC), Pasqual Maragall Foundation, Sant Martí, Barcelona, Spain.
Aida Fernández-LebreroBarcelonaβeta Brain Research Center (BBRC), Pasqual Maragall Foundation, Sant Martí, Barcelona, Spain.
Albert Puig-PijoanDepartment of Neurology, Hospital del Mar Research Institute, Ciutat Vella, Barcelona, Spain.
Paula Ortiz-RomeroBarcelonaβeta Brain Research Center (BBRC), Pasqual Maragall Foundation, Sant Martí, Barcelona, Spain.
Esther Jiménez-MoyanoBarcelonaβeta Brain Research Center (BBRC), Pasqual Maragall Foundation, Sant Martí, Barcelona, Spain.
Carolina MinguillónBarcelonaβeta Brain Research Center (BBRC), Pasqual Maragall Foundation, Sant Martí, Barcelona, Spain.
Marta Del CampoNeurochemistry Laboratory, Department of Laboratory Medicine, Amsterdam Neuroscience, Amsterdam University Medical Center, Vrije Universiteit, Amsterdam, the Netherlands.
Charlotte TeunissenNeurochemistry Laboratory, Department of Laboratory Medicine, Amsterdam Neuroscience, Amsterdam University Medical Center, Vrije Universiteit, Amsterdam, the Netherlands.ORCID 0000-0002-4061-0837

Funding

Alzheimer AssociationAlzheimer Drug Discovery FoundationAlzheimer NetherlandsCure Alzheimer's fundDutch National Dementia StrategyDutch Research CouncilERA PerMed ERAPERMED2021-184European CommissionEuropean Research Council ADG-101096455European Union's Horizon Europe ResearchGHR FoundationHealth HollandInnovation ProgrammeInnovative Medicines Initiatives 3TRKnut and Alice Wallenberg foundation 2022-0231Konung Gustaf V:s och Drottning Victorias FrimurarestiftelseLCF/PR/GN17/50300004 SGR 00913LCF/PR/GN17/50300004 TriBEKa-17-519007Lund UniversityMarie Curie International Training Network)Parkinson foundation of Sweden 1412/22Regionalt Forskningsstöd 2022-1259Regionalt Forskningsstöd 2022-Projekt0080Rönström Family FoundationSkåne University Hospital Foundation 2020-O000028Strategic Research Area MultiParkSwedish Alzheimer Foundation AF-980907Swedish Brain Foundation FO2021-0293Swedish Research Council 2022-00775The Selfridges Group Foundation
6 · The paper itself

Abstract

introductionPlasma phosphorylated tau (p-tau)181, glial fibrillary acidic protein (GFAP), neurofilament light chain (NfL), and amyloid beta ratio (Aβ42/40) may have diagnostic and prognostic value in Alzheimer's disease (AD). Here we assess which markers can best identify AD from controls and other non-AD dementias in a large international multi-center study.

methodsPlasma samples (n = 1298) were collected from six international centers. Aβ40, Aβ42, GFAP, NfL, and p-tau181 were measured using single molecule array. In each group, AD diagnosis/co-pathology was defined according to cerebrospinal fluid biomarkers or amyloid positron emission tomography. Validations were performed in three separate cohorts via single and dual cut-off models.

resultsp-tau181 showed the best area under the curve value to separate AD from frontotemporal dementia, controls, and Aβ- dementia with Lewy bodies. However, this discriminative power could not be reproduced by applying pre-defined cut-offs. DISCUSSION: p-tau181 was the best single plasma marker for detecting AD at any stage. Specific cut-offs are needed to maximize diagnostic performances. HIGHLIGHTS: Phosphorylated tau (p-tau)181 provided a clear differentiation between controls and Alzheimer's disease (AD) participants, with evidence of increased levels in the preclinical stage of AD. Plasma biomarkers demonstrated that when amyloid co-pathology is removed from dementia with Lewy bodies (DLB), only glial fibrillary acidic protein and neurofilament light chain remain to predict DLB. Given the low prevalence of amyloid co-pathology in frontotemporal dementia (FTD), p-tau181 and its ratio with amyloid beta 42 are strong biomarkers to differentiate FTD from AD.

Indexed as

Alzheimer DiseaseAmyloid beta-PeptidesDementiaGlial Fibrillary Acidic ProteinNeurofilament ProteinsPeptide Fragmentstau ProteinsAgedBiomarkersFemaleHumansMaleMiddle AgedPhosphorylationAmyloid beta-Peptidesamyloid beta-protein (1-40)amyloid beta-protein (1-42)BiomarkersGFAP protein, humanGlial Fibrillary Acidic Proteinneurofilament protein LNeurofilament ProteinsPeptide Fragmentstau ProteinsAlzheimer's diseaseamyloid betadementia with Lewy bodiesfrontotemporal dementiaplasma biomarkers

Identifiers

PMID40551285
PMCPMC12185245

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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.