Evidence map›Paper›PMID 41025225›Full record

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

Evidence-based standardized sample handling protocol for accurate blood-based Alzheimer's disease biomarker measurement: Results and consensus of the Global Biomarker Standardization Consortium.

Inge M W Verberk, Mariam Gouda, Daniel Antwi-Berko, Mardou van Leeuwenstijn, Bram Bongers, Isabel M Houtkamp, Wiesje M van der Flier, Shorena Janelidze, Oskar Hansson, Nathalie Le Bastard and 10 more

Abstract readConsensus Statement
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 24 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
24citing 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

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

  1. Pooled it
  2. Article
  3. Review
  4. Review
  5. Brain-derived plasma p-tau217 shows enhanced dynamic range for Alzheimer's disease neuropathological change.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026
    Article
  6. Article
  7. Article
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  9. Multicenter validation of plasma p-tau217/ amyloid beta 1-42 ratio in symptomatic Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026
    Article
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  11. Article
  12. Review
  13. Article
  14. Article
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  16. Article
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  18. Review
  19. Special Issue: "New Insights of Biomarkers in Neurodegenerative Diseases".International journal of molecular sciences · 2025
    Article
  20. Review
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

20 authors.

Inge M W VerberkNeurochemistry Laboratory, Laboratory Medicine, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam Neuroscience, Amsterdam, the Netherlands.
Mariam GoudaNeurochemistry Laboratory, Laboratory Medicine, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam Neuroscience, Amsterdam, the Netherlands.ORCID 0009-0003-4187-3131
Daniel Antwi-BerkoNeurochemistry Laboratory, Laboratory Medicine, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam Neuroscience, Amsterdam, the Netherlands.
Mardou van LeeuwenstijnAlzheimer Center Amsterdam, Neurology, Vrije Universiteit Amsterdam, Amsterdam UMC location VUmc, Amsterdam, the Netherlands.
Bram BongersNeurochemistry Laboratory, Laboratory Medicine, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam Neuroscience, Amsterdam, the Netherlands.
Isabel M HoutkampNeurochemistry Laboratory, Laboratory Medicine, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam Neuroscience, Amsterdam, the Netherlands.
Wiesje M van der FlierAlzheimer Center Amsterdam, Neurology, Vrije Universiteit Amsterdam, Amsterdam UMC location VUmc, Amsterdam, the Netherlands.
Shorena JanelidzeDepartment of Clinical Sciences, Clinical Memory Research Unit, Lund University, Lund, Sweden.
Oskar HanssonDepartment of Clinical Sciences, Clinical Memory Research Unit, Lund University, Lund, Sweden.
Nathalie Le BastardFuijirebio Europe N.V., Ghent, Belgium.
Manu VandijckFuijirebio Europe N.V., Ghent, Belgium.
Jacob HunterALZpath, Carlsbad, California, USA.
Lee HonigbergALZpath, Carlsbad, California, USA.
Kristopher M KirmessC2N Diagnostics LLC, St Louis, Missouri, USA.
Philip B VergheseC2N Diagnostics LLC, St Louis, Missouri, USA.
Kaj BlennowInstitute of Neuroscience and Physiology, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden.
Henrik ZetterbergInstitute of Neuroscience and Physiology, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden.
Emily A MeyersAlzheimer's Association, Chicago, Illinois, USA.
Rebecca M EdelmayerAlzheimer's Association, Chicago, Illinois, USA.
Charlotte TeunissenNeurochemistry Laboratory, Laboratory Medicine, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam Neuroscience, Amsterdam, the Netherlands.

Funding

AD Strategic Fund and the Alzheimer's Association ADSF-21-831376-CAD Strategic Fund and the Alzheimer's Association ADSF-21-831377-CAD Strategic Fund and the Alzheimer's Association ADSF-21-831381-CAD Strategic Fund and the Alzheimer's Association ADSF-24-1284328-CAlzheimer Drug Discovery FoundationAlzheimer NetherlandsAlzheimer's Association 2021 Zenith Award(bPRIDE, CCAD), European Partnership on MetrologyCure Alzheimer's FundDutch National Dementia StrategyEuropean Commission (Marie Curie International Training Network 101119596European Commission (Marie Curie International Training Network 860197 (MIRIADEEuropean Union Joint Program for Neurodegenerative DisordersEuropean Union Joint Programme - Neurodegenerative Disease Research JPND2021-00694European Union's Horizon Europe Research and Innovation Programme 101053962Familjen Beiglers StiftelseFamiljen Rönströms StiftelseHealth HollandHealth Holland, the Dutch Research Council (ZonMW)Hjärnfonden, Sweden ALZ2022-0006Hjärnfonden, Sweden FO2024-0048-HK-24Hjärnfonden, Sweden FO2024-0048-TK-130Innovative Medicines Initiatives 3TRKirsten and Freddy Johansen FoundationLa Fondation Recherche Alzheimer (FRA)Marie Skłodowska-Curie 860197Michael J. Fox FoundationNational Institute for Health and Care Research University College London Hospitals Biomedical Research CentreOlav Thon Foundation, the Erling-Persson Family FoundationPasman Stichting. Research of Alzheimer Center Amsterdamresearch grants of Health Holland and ZonMWSelfridges Group FoundationStichting Alzheimer Nederland and Stichting Steun Alzheimercentrum AmsterdamStiftelsen för Gamla TjänarinnorSwedish Alzheimer Foundation AF-930351Swedish Alzheimer Foundation AF-939721Swedish Alzheimer Foundation AF-968270Swedish Alzheimer Foundation AF-994551Swedish Research Council 2017-00915Swedish Research Council 2022-00732Swedish State Support for Clinical Researchthe Alzheimer Drug Discovery Foundation 201809-2016862the European Partnership on MetrologyTopsector Life Sciences & Health LSHM20106
6 · The paper itself

Abstract

introductionBlood-based biomarkers (BBMs) have revolutionized Alzheimer's disease diagnosis and monitoring. Their pre-analytical stability requires scrutiny. This study assessed pre-analytical effects to inform a standardized sample handling protocol.

methodsAssessed pre-analytical variations included collection tube type, hemolysis, centrifugation settings, centrifugation/storage delays, tube transfers, and freeze-thawing (n = 15/experiment). Phosphorylated tau (pTau) isoforms were measured with Simoa, Lumipulse, MesoScale Discovery, and immunoprecipitation-mass spectrometry. Amyloid-beta (Aβ42, Aβ40), glial fibrillary acidic protein (GFAP), and neurofilament light (NfL) protein were measured with Simoa.

resultsAll assessed BBM levels varied by over 10% by collection tube type. Aβ peptides were the most sensitive, and their levels declined >by more than 10% under storage and centrifugation delays, more steeply at room temperature (RT) compared with 2°C to 8°C. NfL and GFAP levels increased by more than 10% upon RT/-20°C storage. pTau isoforms demonstrated stability across most pre-analytical variations. DISCUSSION: We established an evidence-based handling protocol to ensure reliable sample handling for neurological BBMs upon adoption in clinics, trials, and research. HIGHLIGHTS: Sample handling protocols can mitigate pre-analytical effects on BBM results. We developed an evidence-based, expert-consensus plasma sample handling protocol. Primary collection tube and delays to centrifuging or freezing impact AD BBMs. Plasma pTau217 is highly resistant to pre-analytical sample handling variations. Plasma Aβ42 and Aβ40 were most sensitive to pre-analytical variations.

Indexed as

Alzheimer DiseaseBiomarkersBlood Specimen CollectionSpecimen HandlingAmyloid beta-PeptidesGlial Fibrillary Acidic ProteinHumansNeurofilament ProteinsPeptide Fragmentstau ProteinsAmyloid beta-PeptidesBiomarkersGlial Fibrillary Acidic Proteinneurofilament protein LNeurofilament ProteinsPeptide Fragmentstau Proteinsamyloid betaglial fibrillary acidic proteinneurofilament lightphosphorylated tauplasma biomarkerspre‐analytical variabilitypre‐analyticssample handlingstability

Identifiers

PMID41025225
PMCPMC12481164

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Registered trials

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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.