Evidence map›Paper›PMID 33677733›Full record

ReviewEuropean journal of nuclear medicine and molecular imaging2021

The validation status of blood biomarkers of amyloid and phospho-tau assessed with the 5-phase development framework for AD biomarkers.

N J Ashton, A Leuzy, T K Karikari, N Mattsson-Carlgren, A Dodich, M Boccardi, J Corre, A Drzezga, A Nordberg, R Ossenkoppele and 5 more

Open access · hybridAbstract readReview
PubMed Full text at PMC Publisher
In one paragraph

Review in European journal of nuclear medicine and molecular imaging, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 77 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
77citing papers in PubMed, 1 pooled it
20.9field-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.

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

77 citing papers in PubMed, 1 synthesis or guideline pooled it, 153 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Article
  4. Validating plasma biomarkers for distinguishing neurodegenerative and psychiatric disorders.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026
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  10. The roles of biomarkers in Alzheimer's disease clinical trials.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026
    Review
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  18. Pathologic and cognitive correlates of plasma biomarkers in neurodegenerative disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024
    Article
  19. Article
  20. Article

17 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

15 authors at 8 institutions in 7 countries.

N J AshtonInstitute of Neuroscience & Physiology, Department of Psychiatry & Neurochemistry, Sahlgrenska Academy, University of Gothenburg, House V3/SU, SE-431 80, Mölndal, Sweden. nicholas.ashton@gu.se.ORCID http://orcid.org/0000-0002-3579-8804
A LeuzyClinical Memory Research Unit, Department of Clinical Sciences, Malmö, Lund University, Lund, Sweden.
T K KarikariInstitute of Neuroscience & Physiology, Department of Psychiatry & Neurochemistry, Sahlgrenska Academy, University of Gothenburg, House V3/SU, SE-431 80, Mölndal, Sweden.
N Mattsson-CarlgrenClinical Memory Research Unit, Department of Clinical Sciences, Malmö, Lund University, Lund, Sweden.
A DodichNIMTlab - Neuroimaging and Innovative Molecular Tracers Laboratory, University of Geneva, Geneva, Switzerland.
M BoccardiGerman Center for Neurodegenerative Diseases (DZNE), Rostock-Greifswald, Rostock, Germany.
J CorreCentre National de la Recherche Scientifique, Montpellier, France.
A DrzezgaMedical Faculty and University Hospital of Cologne, Cologne, Germany.
A NordbergDivision of Clinical Geriatrics, Center for Alzheimer Research, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden.
R OssenkoppeleClinical Memory Research Unit, Department of Clinical Sciences, Malmö, Lund University, Lund, Sweden.
H ZetterbergInstitute of Neuroscience & Physiology, Department of Psychiatry & Neurochemistry, Sahlgrenska Academy, University of Gothenburg, House V3/SU, SE-431 80, Mölndal, Sweden.
K BlennowInstitute of Neuroscience & Physiology, Department of Psychiatry & Neurochemistry, Sahlgrenska Academy, University of Gothenburg, House V3/SU, SE-431 80, Mölndal, Sweden.
G B FrisoniGerman Center for Neurodegenerative Diseases (DZNE), Rostock-Greifswald, Rostock, Germany.
V GaribottoNIMTlab - Neuroimaging and Innovative Molecular Tracers Laboratory, University of Geneva, Geneva, Switzerland.
O HanssonClinical Memory Research Unit, Department of Clinical Sciences, Malmö, Lund University, Lund, Sweden. Oskar.Hansson@med.lu.se.
Lund University · SEUniversity of Geneva · CHSahlgrenska University Hospital · SEGerman Center for Neurodegenerative Diseases · DEKarolinska University Hospital · SEKing's College London · GBUniversity Hospital Cologne · DEUniversity of Gothenburg · SE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

purposeThe development of blood biomarkers that reflect Alzheimer's disease (AD) pathophysiology (phosphorylated tau and amyloid-β) has offered potential as scalable tests for dementia differential diagnosis and early detection. In 2019, the Geneva AD Biomarker Roadmap Initiative included blood biomarkers in the systematic validation of AD biomarkers.

methodsA panel of experts convened in November 2019 at a two-day workshop in Geneva. The level of maturity (fully achieved, partly achieved, preliminary evidence, not achieved, unsuccessful) of blood biomarkers was assessed based on the Biomarker Roadmap methodology and discussed fully during the workshop which also evaluated cerebrospinal fluid (CSF) and positron emission tomography (PET) biomarkers.

resultsPlasma p-tau has shown analytical validity (phase 2 primary aim 1) and first evidence of clinical validity (phase 3 primary aim 1), whereas the maturity level for Aβ remains to be partially achieved. Full and partial achievement has been assigned to p-tau and Aβ, respectively, in their associations to ante-mortem measures (phase 2 secondary aim 2). However, only preliminary evidence exists for the influence of covariates, assay comparison and cut-off criteria.

conclusionsDespite the relative infancy of blood biomarkers, in comparison to CSF biomarkers, much has already been achieved for phases 1 through 3 - with p-tau having greater success in detecting AD and predicting disease progression. However, sufficient data about the effect of covariates on the biomarker measurement is lacking. No phase 4 (real-world performance) or phase 5 (assessment of impact/cost) aim has been tested, thus not achieved.

Indexed as

Alzheimer DiseaseAmyloid beta-PeptidesBiomarkersHumansPeptide Fragmentstau ProteinsTomography, X-Ray ComputedAmyloid beta-PeptidesBiomarkersPeptide Fragmentstau ProteinsAlzheimer’s diseaseAβ40Aβ42BloodP-tauStrategic roadmap

Identifiers

PMID33677733
PMCPMC8175325
OpenAlexW3135004658

What OpenQuestion holds

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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.