ArticleNeurology(R) neuroimmunology & neuroinflammation2025
Temporal Dynamics of Plasma Neurofilament Light in Blood Donors With Preclinical Multiple Sclerosis.
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Article in Neurology(R) neuroimmunology & neuroinflammation, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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12 citing papers in PubMed.
- The presynaptic protein bassoon is a biofluid biomarker of synaptic pathology in multiple sclerosis.EBioMedicine · 2026Article
- Evaluation of potential serum biomarkers for individuals at risk of multiple sclerosis.bioRxiv : the preprint server for biology · 2026Article
- Towards primary prevention of multiple sclerosis.Nature reviews. Neurology · 2026Review
- Toward a global research agenda for preventing multiple sclerosis.Multiple sclerosis (Houndmills, Basingstoke, England) · 2026Article
- Myelin injury precedes axonal injury and symptomatic onset in multiple sclerosis.Nature medicine · 2026Article
- Health care use preceding pediatric multiple sclerosis: A population-based study from Ontario, Canada.Multiple sclerosis (Houndmills, Basingstoke, England) · 2025Article
- Phenotyping Healthcare Use 2-3 Decades Before the First Multiple Sclerosis Demyelinating Event.Annals of clinical and translational neurology · 2025Article
- Longitudinal evaluation of serum neurofilament light levels in normal healthy volunteers: defining a threshold of concern.Journal of neurology · 2025Article
- Multiple sclerosis: 2024 update.Free neuropathology · 2025Review
- A role of CD20Frontiers in immunology · 2025Article
- A multimodal approach to distinguish multiple sclerosis phenotypes at diagnosis using biomarker profiles.Therapeutic advances in neurological disorders · 2025Article
- Ethics of disclosure of onset-predictive biomarker test results for genetic frontotemporal dementia in the research context.Alzheimer's & dementia (Amsterdam, Netherlands)Article
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Authors and funding
14 authors.
Josefine BritzeFrom the The Danish Multiple Sclerosis Centre (J.B., H.B.S., M.M., J.L.F.B., F.S.), Department of Neurology, Copenhagen University Hospital, Rigshospitalet; Department of Clinical Immunology (J.B., M.H.L., S.R.O., S.M.), Copenhagen University Hospital Rigshospitalet; Department of Clinical Medicine (J.B., M.M., O.B.P., S.R.O., J.L.F.B., F.S., S.M.), Faculty of Health and Medical Sciences, University of Copenhagen; Department of Health Technology (A.G.P.), Section for Bioinformatics, Technical University of Denmark; The Danish Cancer Institute (S.R.), Statistics and Data Analysis; The Danish Multiple Sclerosis Registry (M.M.); Department of Clinical Immunology (O.B.P.), Zealand University Hospital; Department of Clinical Immunology (B.A.J.), Aalborg University Teaching Hospital; Department of Clinical Immunology (C.E.), Aarhus University Teaching Hospital and Statens Serum Institut (H.U.), Copenhagen, Denmark.
Margit Hørup LarsenFrom the The Danish Multiple Sclerosis Centre (J.B., H.B.S., M.M., J.L.F.B., F.S.), Department of Neurology, Copenhagen University Hospital, Rigshospitalet; Department of Clinical Immunology (J.B., M.H.L., S.R.O., S.M.), Copenhagen University Hospital Rigshospitalet; Department of Clinical Medicine (J.B., M.M., O.B.P., S.R.O., J.L.F.B., F.S., S.M.), Faculty of Health and Medical Sciences, University of Copenhagen; Department of Health Technology (A.G.P.), Section for Bioinformatics, Technical University of Denmark; The Danish Cancer Institute (S.R.), Statistics and Data Analysis; The Danish Multiple Sclerosis Registry (M.M.); Department of Clinical Immunology (O.B.P.), Zealand University Hospital; Department of Clinical Immunology (B.A.J.), Aalborg University Teaching Hospital; Department of Clinical Immunology (C.E.), Aarhus University Teaching Hospital and Statens Serum Institut (H.U.), Copenhagen, Denmark.
Anders Gorm PedersenFrom the The Danish Multiple Sclerosis Centre (J.B., H.B.S., M.M., J.L.F.B., F.S.), Department of Neurology, Copenhagen University Hospital, Rigshospitalet; Department of Clinical Immunology (J.B., M.H.L., S.R.O., S.M.), Copenhagen University Hospital Rigshospitalet; Department of Clinical Medicine (J.B., M.M., O.B.P., S.R.O., J.L.F.B., F.S., S.M.), Faculty of Health and Medical Sciences, University of Copenhagen; Department of Health Technology (A.G.P.), Section for Bioinformatics, Technical University of Denmark; The Danish Cancer Institute (S.R.), Statistics and Data Analysis; The Danish Multiple Sclerosis Registry (M.M.); Department of Clinical Immunology (O.B.P.), Zealand University Hospital; Department of Clinical Immunology (B.A.J.), Aalborg University Teaching Hospital; Department of Clinical Immunology (C.E.), Aarhus University Teaching Hospital and Statens Serum Institut (H.U.), Copenhagen, Denmark.
Susanne RosthøjFrom the The Danish Multiple Sclerosis Centre (J.B., H.B.S., M.M., J.L.F.B., F.S.), Department of Neurology, Copenhagen University Hospital, Rigshospitalet; Department of Clinical Immunology (J.B., M.H.L., S.R.O., S.M.), Copenhagen University Hospital Rigshospitalet; Department of Clinical Medicine (J.B., M.M., O.B.P., S.R.O., J.L.F.B., F.S., S.M.), Faculty of Health and Medical Sciences, University of Copenhagen; Department of Health Technology (A.G.P.), Section for Bioinformatics, Technical University of Denmark; The Danish Cancer Institute (S.R.), Statistics and Data Analysis; The Danish Multiple Sclerosis Registry (M.M.); Department of Clinical Immunology (O.B.P.), Zealand University Hospital; Department of Clinical Immunology (B.A.J.), Aalborg University Teaching Hospital; Department of Clinical Immunology (C.E.), Aarhus University Teaching Hospital and Statens Serum Institut (H.U.), Copenhagen, Denmark.
Helle Bach SøndergaardFrom the The Danish Multiple Sclerosis Centre (J.B., H.B.S., M.M., J.L.F.B., F.S.), Department of Neurology, Copenhagen University Hospital, Rigshospitalet; Department of Clinical Immunology (J.B., M.H.L., S.R.O., S.M.), Copenhagen University Hospital Rigshospitalet; Department of Clinical Medicine (J.B., M.M., O.B.P., S.R.O., J.L.F.B., F.S., S.M.), Faculty of Health and Medical Sciences, University of Copenhagen; Department of Health Technology (A.G.P.), Section for Bioinformatics, Technical University of Denmark; The Danish Cancer Institute (S.R.), Statistics and Data Analysis; The Danish Multiple Sclerosis Registry (M.M.); Department of Clinical Immunology (O.B.P.), Zealand University Hospital; Department of Clinical Immunology (B.A.J.), Aalborg University Teaching Hospital; Department of Clinical Immunology (C.E.), Aarhus University Teaching Hospital and Statens Serum Institut (H.U.), Copenhagen, Denmark.ORCID 0000-0001-9435-0658
Melinda MagyariFrom the The Danish Multiple Sclerosis Centre (J.B., H.B.S., M.M., J.L.F.B., F.S.), Department of Neurology, Copenhagen University Hospital, Rigshospitalet; Department of Clinical Immunology (J.B., M.H.L., S.R.O., S.M.), Copenhagen University Hospital Rigshospitalet; Department of Clinical Medicine (J.B., M.M., O.B.P., S.R.O., J.L.F.B., F.S., S.M.), Faculty of Health and Medical Sciences, University of Copenhagen; Department of Health Technology (A.G.P.), Section for Bioinformatics, Technical University of Denmark; The Danish Cancer Institute (S.R.), Statistics and Data Analysis; The Danish Multiple Sclerosis Registry (M.M.); Department of Clinical Immunology (O.B.P.), Zealand University Hospital; Department of Clinical Immunology (B.A.J.), Aalborg University Teaching Hospital; Department of Clinical Immunology (C.E.), Aarhus University Teaching Hospital and Statens Serum Institut (H.U.), Copenhagen, Denmark.ORCID 0000-0002-0972-5222
Ole Birger PedersenFrom the The Danish Multiple Sclerosis Centre (J.B., H.B.S., M.M., J.L.F.B., F.S.), Department of Neurology, Copenhagen University Hospital, Rigshospitalet; Department of Clinical Immunology (J.B., M.H.L., S.R.O., S.M.), Copenhagen University Hospital Rigshospitalet; Department of Clinical Medicine (J.B., M.M., O.B.P., S.R.O., J.L.F.B., F.S., S.M.), Faculty of Health and Medical Sciences, University of Copenhagen; Department of Health Technology (A.G.P.), Section for Bioinformatics, Technical University of Denmark; The Danish Cancer Institute (S.R.), Statistics and Data Analysis; The Danish Multiple Sclerosis Registry (M.M.); Department of Clinical Immunology (O.B.P.), Zealand University Hospital; Department of Clinical Immunology (B.A.J.), Aalborg University Teaching Hospital; Department of Clinical Immunology (C.E.), Aarhus University Teaching Hospital and Statens Serum Institut (H.U.), Copenhagen, Denmark.
Bitten Aagaard JensenFrom the The Danish Multiple Sclerosis Centre (J.B., H.B.S., M.M., J.L.F.B., F.S.), Department of Neurology, Copenhagen University Hospital, Rigshospitalet; Department of Clinical Immunology (J.B., M.H.L., S.R.O., S.M.), Copenhagen University Hospital Rigshospitalet; Department of Clinical Medicine (J.B., M.M., O.B.P., S.R.O., J.L.F.B., F.S., S.M.), Faculty of Health and Medical Sciences, University of Copenhagen; Department of Health Technology (A.G.P.), Section for Bioinformatics, Technical University of Denmark; The Danish Cancer Institute (S.R.), Statistics and Data Analysis; The Danish Multiple Sclerosis Registry (M.M.); Department of Clinical Immunology (O.B.P.), Zealand University Hospital; Department of Clinical Immunology (B.A.J.), Aalborg University Teaching Hospital; Department of Clinical Immunology (C.E.), Aarhus University Teaching Hospital and Statens Serum Institut (H.U.), Copenhagen, Denmark.
Sisse Rye OstrowskiFrom the The Danish Multiple Sclerosis Centre (J.B., H.B.S., M.M., J.L.F.B., F.S.), Department of Neurology, Copenhagen University Hospital, Rigshospitalet; Department of Clinical Immunology (J.B., M.H.L., S.R.O., S.M.), Copenhagen University Hospital Rigshospitalet; Department of Clinical Medicine (J.B., M.M., O.B.P., S.R.O., J.L.F.B., F.S., S.M.), Faculty of Health and Medical Sciences, University of Copenhagen; Department of Health Technology (A.G.P.), Section for Bioinformatics, Technical University of Denmark; The Danish Cancer Institute (S.R.), Statistics and Data Analysis; The Danish Multiple Sclerosis Registry (M.M.); Department of Clinical Immunology (O.B.P.), Zealand University Hospital; Department of Clinical Immunology (B.A.J.), Aalborg University Teaching Hospital; Department of Clinical Immunology (C.E.), Aarhus University Teaching Hospital and Statens Serum Institut (H.U.), Copenhagen, Denmark.
Christian ErikstrupFrom the The Danish Multiple Sclerosis Centre (J.B., H.B.S., M.M., J.L.F.B., F.S.), Department of Neurology, Copenhagen University Hospital, Rigshospitalet; Department of Clinical Immunology (J.B., M.H.L., S.R.O., S.M.), Copenhagen University Hospital Rigshospitalet; Department of Clinical Medicine (J.B., M.M., O.B.P., S.R.O., J.L.F.B., F.S., S.M.), Faculty of Health and Medical Sciences, University of Copenhagen; Department of Health Technology (A.G.P.), Section for Bioinformatics, Technical University of Denmark; The Danish Cancer Institute (S.R.), Statistics and Data Analysis; The Danish Multiple Sclerosis Registry (M.M.); Department of Clinical Immunology (O.B.P.), Zealand University Hospital; Department of Clinical Immunology (B.A.J.), Aalborg University Teaching Hospital; Department of Clinical Immunology (C.E.), Aarhus University Teaching Hospital and Statens Serum Institut (H.U.), Copenhagen, Denmark.ORCID 0000-0001-6551-6647
Henrik UllumFrom the The Danish Multiple Sclerosis Centre (J.B., H.B.S., M.M., J.L.F.B., F.S.), Department of Neurology, Copenhagen University Hospital, Rigshospitalet; Department of Clinical Immunology (J.B., M.H.L., S.R.O., S.M.), Copenhagen University Hospital Rigshospitalet; Department of Clinical Medicine (J.B., M.M., O.B.P., S.R.O., J.L.F.B., F.S., S.M.), Faculty of Health and Medical Sciences, University of Copenhagen; Department of Health Technology (A.G.P.), Section for Bioinformatics, Technical University of Denmark; The Danish Cancer Institute (S.R.), Statistics and Data Analysis; The Danish Multiple Sclerosis Registry (M.M.); Department of Clinical Immunology (O.B.P.), Zealand University Hospital; Department of Clinical Immunology (B.A.J.), Aalborg University Teaching Hospital; Department of Clinical Immunology (C.E.), Aarhus University Teaching Hospital and Statens Serum Institut (H.U.), Copenhagen, Denmark.
Jette Lautrup Frederiksen BattistiniFrom the The Danish Multiple Sclerosis Centre (J.B., H.B.S., M.M., J.L.F.B., F.S.), Department of Neurology, Copenhagen University Hospital, Rigshospitalet; Department of Clinical Immunology (J.B., M.H.L., S.R.O., S.M.), Copenhagen University Hospital Rigshospitalet; Department of Clinical Medicine (J.B., M.M., O.B.P., S.R.O., J.L.F.B., F.S., S.M.), Faculty of Health and Medical Sciences, University of Copenhagen; Department of Health Technology (A.G.P.), Section for Bioinformatics, Technical University of Denmark; The Danish Cancer Institute (S.R.), Statistics and Data Analysis; The Danish Multiple Sclerosis Registry (M.M.); Department of Clinical Immunology (O.B.P.), Zealand University Hospital; Department of Clinical Immunology (B.A.J.), Aalborg University Teaching Hospital; Department of Clinical Immunology (C.E.), Aarhus University Teaching Hospital and Statens Serum Institut (H.U.), Copenhagen, Denmark.
Finn SellebjergFrom the The Danish Multiple Sclerosis Centre (J.B., H.B.S., M.M., J.L.F.B., F.S.), Department of Neurology, Copenhagen University Hospital, Rigshospitalet; Department of Clinical Immunology (J.B., M.H.L., S.R.O., S.M.), Copenhagen University Hospital Rigshospitalet; Department of Clinical Medicine (J.B., M.M., O.B.P., S.R.O., J.L.F.B., F.S., S.M.), Faculty of Health and Medical Sciences, University of Copenhagen; Department of Health Technology (A.G.P.), Section for Bioinformatics, Technical University of Denmark; The Danish Cancer Institute (S.R.), Statistics and Data Analysis; The Danish Multiple Sclerosis Registry (M.M.); Department of Clinical Immunology (O.B.P.), Zealand University Hospital; Department of Clinical Immunology (B.A.J.), Aalborg University Teaching Hospital; Department of Clinical Immunology (C.E.), Aarhus University Teaching Hospital and Statens Serum Institut (H.U.), Copenhagen, Denmark.ORCID 0000-0002-1333-9623
Signe ModvigFrom the The Danish Multiple Sclerosis Centre (J.B., H.B.S., M.M., J.L.F.B., F.S.), Department of Neurology, Copenhagen University Hospital, Rigshospitalet; Department of Clinical Immunology (J.B., M.H.L., S.R.O., S.M.), Copenhagen University Hospital Rigshospitalet; Department of Clinical Medicine (J.B., M.M., O.B.P., S.R.O., J.L.F.B., F.S., S.M.), Faculty of Health and Medical Sciences, University of Copenhagen; Department of Health Technology (A.G.P.), Section for Bioinformatics, Technical University of Denmark; The Danish Cancer Institute (S.R.), Statistics and Data Analysis; The Danish Multiple Sclerosis Registry (M.M.); Department of Clinical Immunology (O.B.P.), Zealand University Hospital; Department of Clinical Immunology (B.A.J.), Aalborg University Teaching Hospital; Department of Clinical Immunology (C.E.), Aarhus University Teaching Hospital and Statens Serum Institut (H.U.), Copenhagen, Denmark.ORCID 0000-0001-9113-1097
Funding
No grant is acknowledged in the PubMed record.
Abstract
BACKGROUND AND
objectivesMultiple sclerosis (MS) is a CNS disease, characterized by demyelination, inflammation, and neurodegeneration. Recent advances in technology allow measurement of the axonal damage marker neurofilament light chain in peripheral blood. Two studies have shown that patients with MS have elevated neurofilament light levels before their first symptom, but longitudinal studies are lacking. We aimed to investigate the intraindividual neurofilament light dynamics during the presymptomatic phase of MS.
methodsThe Danish Blood Donor Study (DBDS) has stored plasma samples from blood donors for more than 10 years. We identified DBDS participants, who had subsequently been diagnosed with MS, and included all samples donated before their first demyelinating symptom (median 5.00 samples per case). As controls, we included 2 healthy donors per case. Plasma levels of neurofilament light were measured and compared with quality-of-life data. We used a Bayesian approach to derive estimates for the percentage of cases with presymptomatic increased neurofilament light levels.
resultsWe observed that 12 (17%, 95% CI 9%-28%) of 69 presymptomatic MS donors had intermittently increased neurofilament light levels preclinically. Increased levels were present up to 9 years before clinical onset, also in primary progressive MS. Healthy donors and presymptomatic MS donors with and without increased neurofilament light levels reported equally high physical and mental well-being. Model-based estimates suggested that 55% of cases (95% credible interval [28%-87%]) had experienced increased presymptomatic neurofilament light levels. DISCUSSION: Patients with MS periodically sustain axonal injury up to 9 years before clinical onset, even in primary progressive disease. This most likely represents asymptomatic disease activity. Some or even all patients are affected by this intermittent axonal injury, prompting the need for further studies of the presymptomatic phase in relation to prognosis and as a therapeutic window of opportunity.
Indexed as
Blood DonorsMultiple SclerosisNeurofilament ProteinsAdultAsymptomatic DiseasesBiomarkersDenmarkFemaleHumansLongitudinal StudiesMaleMiddle AgedProdromal SymptomsYoung AdultBiomarkersneurofilament protein LNeurofilament Proteins
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