Evidence map›Paper›PMID 34099648›Full record

ArticleNature communications2021

A multicentre validation study of the diagnostic value of plasma neurofilament light.

Nicholas J Ashton, Shorena Janelidze, Ahmad Al Khleifat, Antoine Leuzy, Emma L van der Ende, Thomas K Karikari, Andrea L Benedet, Tharick A Pascoal, Alberto Lleó, Lucilla Parnetti and 31 more

Registry-linked trialOpen access · goldAbstract readMulticenter StudyValidation Study
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT07731191 (Development of Digital Solutions for the Prediction of the Biological Mechanisms of Alzheimer's Disease Through the Analysis of Risk Factors), which is not on this map. Cited by 331 papers, 10 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
331citing papers in PubMed, 10 pooled it
44.5field-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.

NCT07731191 narecruitingnot on this mapstarted 2026, after this paper: background citation

Development of Digital Solutions for the Prediction of the Biological Mechanisms of Alzheimer's Disease Through the Analysis of Risk Factors (PrevAI)

TypeinterventionalSponsorIRCCS Centro San Giovanni di Dio FatebenefratelliRan2026 to 2026Enrolled240ConditionsMild Cognitive Impairment (MCI), Subjective Cognitive Decline (SCD)ArmsDigital solution for the prediction of the biological mechanisms of Alzheimer's disease through the analysis of risk factors
3 · Its place in the literature

Who cites it

331 citing papers in PubMed, 10 syntheses or guidelines pooled it, 537 citations in OpenAlex.

  1. Pooled it
  2. Elevated neurofilament light chain (NfL) in blood and CSF as a biomarker for Parkinson's disease cognitive impairment: A meta-analysis.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2026
    Pooled it
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  4. Systematic Review with Meta-Analysis of Biofluid Markers for Huntington's Disease.Movement disorders : official journal of the Movement Disorder Society · 2025
    Pooled it
  5. Blood-based biomarkers for Alzheimer's disease in Down syndrome: A systematic review and meta-analysis.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025
    Pooled it
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271 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

41 authors at 17 institutions in 8 countries.

Nicholas J AshtonDepartment of Psychiatry and Neurochemistry, Institute of Neuroscience & Physiology, The Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden. nicholas.ashton@gu.se.ORCID 0000-0002-3579-8804
Shorena JanelidzeClinical Memory Research Unit, Department of Clinical Sciences Malmö, Lund University, Lund, Sweden.
Ahmad Al KhleifatDepartment of Basic and Clinical Neuroscience, Maurice Wohl Clinical Neuroscience Institute, King's College London, London, UK.ORCID 0000-0002-7406-9831
Antoine LeuzyClinical Memory Research Unit, Department of Clinical Sciences Malmö, Lund University, Lund, Sweden.
Emma L van der EndeDepartment of Neurology and Alzheimer Center, Erasmus University Medical Center, Rotterdam, Netherlands.
Thomas K KarikariDepartment of Psychiatry and Neurochemistry, Institute of Neuroscience & Physiology, The Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.ORCID 0000-0003-1422-4358
Andrea L BenedetTranslational Neuroimaging Laboratory, The McGill University Research Centre for Studies in Aging, Montreal, QC, Canada.
Tharick A PascoalTranslational Neuroimaging Laboratory, The McGill University Research Centre for Studies in Aging, Montreal, QC, Canada.
Alberto LleóMemory Unit, Department of Neurology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.ORCID 0000-0002-2568-5478
Lucilla ParnettiLaboratory of Clinical Neurochemistry, Neurology Clinic, University of Perugia, Perugia, Italy.
Daniela GalimbertiFondazione IRCCS Ca' Granda, Ospedale Policlinico, Milan, Italy.ORCID 0000-0002-9284-5953
Laura BonanniDepartment of Neuroscience, Imaging and Clinical Sciences, University G.d'Annunzio of Chieti-Pescara, Chieti, Italy.
Andrea PilottoNeurology Unit, Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy.
Alessandro PadovaniNeurology Unit, Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy.
Jan LyckeDepartment of Clinical Neuroscience, Institution of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.ORCID 0000-0002-7891-8466
Lenka NovakovaDepartment of Clinical Neuroscience, Institution of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
Markus AxelssonDepartment of Clinical Neuroscience, Institution of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
Latha VelayudhanDepartment of Old Age Psychiatry, Maurice Wohl Clinical Neuroscience Institute, King's College London, London, UK.ORCID 0000-0002-7712-930X
Gil D RabinoviciDepartment of Neurology, University of California San Francisco, Memory and Aging Center, San Francisco, CA, USA.
Bruce MillerDepartment of Neurology, University of California San Francisco, Memory and Aging Center, San Francisco, CA, USA.
Carmine ParianteStress, Psychiatry and Immunology Lab & Perinatal Psychiatry, Maurice Wohl Clinical Neuroscience Institute, King's College London, London, UK.ORCID 0000-0002-9132-5091
Naghmeh NikkheslatStress, Psychiatry and Immunology Lab & Perinatal Psychiatry, Maurice Wohl Clinical Neuroscience Institute, King's College London, London, UK.
Susan M ResnickBrain Aging and Behavior Section, Laboratory of Behavioral Neuroscience, National Institute on Aging, National Institutes of Health, Baltimore, MD, USA.
Madhav ThambisettyClinical and Translational Neuroscience Section, Laboratory of Behavioral Neuroscience, National Institute on Aging, National Institutes of Health, Baltimore, MD, USA.
Michael SchöllDepartment of Psychiatry and Neurochemistry, Institute of Neuroscience & Physiology, The Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.ORCID 0000-0001-7800-1781
Gorka Fernández-EulateNeurosciences Area, Biodonostia Health Research Institute, San Sebastián, Spain.ORCID 0000-0003-1112-7464
Francisco J Gil-BeaNeurosciences Area, Biodonostia Health Research Institute, San Sebastián, Spain.
Adolfo López de MunainNeurosciences Area, Biodonostia Health Research Institute, San Sebastián, Spain.
Ammar Al-ChalabiDepartment of Basic and Clinical Neuroscience, Maurice Wohl Clinical Neuroscience Institute, King's College London, London, UK.ORCID 0000-0002-4924-7712
Pedro Rosa-NetoTranslational Neuroimaging Laboratory, The McGill University Research Centre for Studies in Aging, Montreal, QC, Canada.
Andre StrydomDepartment of Forensic and Neurodevelopmental Sciences, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
Per SvenningssonDepartment of Old Age Psychiatry, Maurice Wohl Clinical Neuroscience Institute, King's College London, London, UK.
Erik StomrudClinical Memory Research Unit, Department of Clinical Sciences Malmö, Lund University, Lund, Sweden.
Alexander SantilloClinical Memory Research Unit, Department of Clinical Sciences Malmö, Lund University, Lund, Sweden.
Dag AarslandDepartment of Old Age Psychiatry, Maurice Wohl Clinical Neuroscience Institute, King's College London, London, UK.
John C van SwietenDepartment of Neurology and Alzheimer Center, Erasmus University Medical Center, Rotterdam, Netherlands.
Sebastian PalmqvistClinical Memory Research Unit, Department of Clinical Sciences Malmö, Lund University, Lund, Sweden.ORCID 0000-0002-9267-1930
Henrik ZetterbergDepartment of Psychiatry and Neurochemistry, Institute of Neuroscience & Physiology, The Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.ORCID 0000-0003-3930-4354
Kaj BlennowDepartment of Psychiatry and Neurochemistry, Institute of Neuroscience & Physiology, The Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.ORCID 0000-0002-1890-4193
Abdul HyeDepartment of Old Age Psychiatry, Maurice Wohl Clinical Neuroscience Institute, King's College London, London, UK.
Oskar HanssonClinical Memory Research Unit, Department of Clinical Sciences Malmö, Lund University, Lund, Sweden. oskar.hansson@med.lu.se.ORCID 0000-0001-8467-7286
King's College London · GBLund University · SESahlgrenska University Hospital · SEInstituto de Salud Carlos III · ESMontreal Neurological Institute and Hospital · CAErasmus MC · NLNational Institutes of Health · USUniversity of California, San Francisco · USBiogipuzkoa Health Research Institute · ESFondazione Europea Ricerca Biomedica · ITNational Hospital for Neurology and Neurosurgery · GBUniversity of Brescia · ITUniversity of Chieti-Pescara · ITUniversity of Gothenburg · SEUniversity of Leicester · GBUniversity of Milan · ITUniversity of Perugia · IT

Funding

Research Education ComponentP30AG066507 · NIA · JOHNS HOPKINS UNIVERSITY · PI Corinne Pettigrew · 2020 to 2026
$29.3M
Early Markers of Alzheimer DiseaseZIAAG000185 · NIA · NATIONAL INSTITUTE ON AGING · PI WALKER, KEENAN · 2009 to 2025
$20.4M
Understanding mechanisms and seeking novel biomarkers in Alzheimer's diseaseZIAAG000200 · NIA · NATIONAL INSTITUTE ON AGING · PI RESNICK, SUSAN · 2013 to 2024
$12.2M
Department of HealthMedical Research Council G0600974Medical Research Council MR/L501529/1Medical Research Council MR/R024804/1Medical Research Council MR/R024901/1Medical Research Council MR/S005145/1Medical Research Council MR/S011277/1Medical Research Council S011277/1Motor Neurone Disease Association ALCHALABI-DOBSON/APR14/829-791Motor Neurone Disease Association ALCHALABI-TALBOT/APR14/926-794NIA NIH HHS P30 AG066507Wellcome TrustWellcome Trust 098330/Z/12/Z
6 · The paper itself

Abstract

Increased cerebrospinal fluid neurofilament light (NfL) is a recognized biomarker for neurodegeneration that can also be assessed in blood. Here, we investigate plasma NfL as a marker of neurodegeneration in 13 neurodegenerative disorders, Down syndrome, depression and cognitively unimpaired controls from two multicenter cohorts: King's College London (n = 805) and the Swedish BioFINDER study (n = 1,464). Plasma NfL was significantly increased in all cortical neurodegenerative disorders, amyotrophic lateral sclerosis and atypical parkinsonian disorders. We demonstrate that plasma NfL is clinically useful in identifying atypical parkinsonian disorders in patients with parkinsonism, dementia in individuals with Down syndrome, dementia among psychiatric disorders, and frontotemporal dementia in patients with cognitive impairment. Data-driven cut-offs highlighted the fundamental importance of age-related clinical cut-offs for disorders with a younger age of onset. Finally, plasma NfL performs best when applied to indicate no underlying neurodegeneration, with low false positives, in all age-related cut-offs.

Indexed as

AgedAge FactorsBiomarkersCognitive DysfunctionCohort StudiesDepressionDown SyndromeFalse Positive ReactionsFemaleHumansMaleMiddle AgedNeurodegenerative DiseasesNeurofilament ProteinsPredictive Value of TestsReference ValuesBiomarkersneurofilament protein LNeurofilament Proteins

Identifiers

PMID34099648
PMCPMC8185001
OpenAlexW3167068736

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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.