ArticleNeurobiology of disease2020
Serum neurofilament light chain levels are associated with white matter integrity in autosomal dominant Alzheimer's disease.
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Article in Neurobiology of disease, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers, 1 of them a synthesis that pooled it.
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36citing papers in PubMed, 1 pooled it
3.6field-weighted citation impact, top 5% of its field
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Who cites it
36 citing papers in PubMed, 1 synthesis or guideline pooled it, 59 citations in OpenAlex.
- Association between blood-based protein biomarkers and brain MRI in the Alzheimer's disease continuum: a systematic review.Journal of neurology · 2024Pooled it
- Trial
- The Potential Effects of Oxidative Stress-Related Plasma Abnormal Protein Aggregate Levels on Brain Volume and Its Neuropsychiatric Consequences in Parkinson's Disease.Oxidative medicine and cellular longevity · 2021Trial
- Design, Implementation, and Advances in Indirect SERS Sensors for Biomedical and Human-Health-Related Analyte Detection.Sensors (Basel, Switzerland) · 2026Review
- MarkVCID2 Consortium for Clinical Validation of Biomarkers of Cerebral Small Vessel Disease: Validation Framework and Baseline Characteristics.Annals of neurology · 2026Article
- Article
- Understanding Cerebral Blood Flow Dynamics for Alzheimer's Disease Prevention Through Acute Exercise (flADex): Protocol for a Randomized Crossover Trial.Brain and behavior · 2025Article
- Neurofilament Biomarkers in Neurology: From Neuroinflammation to Neurodegeneration, Bridging Established and Novel Analytical Advances with Clinical Practice.International journal of molecular sciences · 2025Review
- Proteomic analysis of Down syndrome cerebrospinal fluid compared to late-onset and autosomal dominant Alzheimer´s disease.Nature communications · 2025Article
- From Cell Architecture to Mitochondrial Signaling: Role of Intermediate Filaments in Health, Aging, and Disease.International journal of molecular sciences · 2025Review
- Comparative neurofilament light chain trajectories in CSF and plasma in autosomal dominant Alzheimer's disease.Nature communications · 2024Observational
- Quantitative Evaluation of White Matter Injury by Cranial Ultrasound to Detect the Effects of Parenteral Nutrition in Preterm Babies: An Observational Study.Journal of imaging · 2024Article
- Characterization of white matter hyperintensities in Down syndrome.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Article
- Neurofilaments Light Chain in Neurodegenerative Dementias: A Review of Imaging Correlates.Brain sciences · 2024Review
- Serum neurofilament light and white matter characteristics in the general population: a longitudinal analysis.GeroScience · 2024Article
- The potential of blood neurofilament light as a marker of neurodegeneration for Alzheimer's disease.Brain : a journal of neurology · 2024Review
- Multi-peptide characterization of plasma neurofilament light chain in preclinical and mild Alzheimer's disease.Brain communications · 2024Article
- Plasma Neurofilament Light Relates to Divergent Default and Salience Network Connectivity in Alzheimer's Disease and Behavioral Variant Frontotemporal Dementia.Journal of Alzheimer's disease : JAD · 2024Article
- The emerging role of blood biomarkers in diagnosis and treatment of Alzheimer's disease.European geriatric medicine · 2023Article
- Cerebrospinal fluid proteomics define the natural history of autosomal dominant Alzheimer's disease.Nature medicine · 2023Article
Corrections and comments
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Authors and funding
48 authors at 18 institutions in 5 countries.
Stephanie A SchultzDepartment of Radiology, Department of Neurology, Department of Pathology & Immunology, Department of Psychiatry, Division of Biostatistics, Washington University in St. Louis School of Medicine, Saint Louis, MO, USA.
Jeremy F StrainDepartment of Radiology, Department of Neurology, Department of Pathology & Immunology, Department of Psychiatry, Division of Biostatistics, Washington University in St. Louis School of Medicine, Saint Louis, MO, USA.
Adedamola AdedokunDepartment of Radiology, Department of Neurology, Department of Pathology & Immunology, Department of Psychiatry, Division of Biostatistics, Washington University in St. Louis School of Medicine, Saint Louis, MO, USA.
Qing WangDepartment of Radiology, Department of Neurology, Department of Pathology & Immunology, Department of Psychiatry, Division of Biostatistics, Washington University in St. Louis School of Medicine, Saint Louis, MO, USA.
Oliver PreischeDZNE-German Center for Neurodegenerative Diseases, D-72076 Tübingen, Germany; Department of Cellular Neurology, Hertie Institute for Clinical Brain Research, University of Tübingen, D-72076 Tübingen, Germany.
Jens KuhleNeurologic Clinic and Policlinic, Departments of Medicine, Biomedicine and Clinical Research, University Hospital Basel, University of Basel, CH-4031 Basel, Switzerland.
Shaney FloresDepartment of Radiology, Department of Neurology, Department of Pathology & Immunology, Department of Psychiatry, Division of Biostatistics, Washington University in St. Louis School of Medicine, Saint Louis, MO, USA.
Sarah KeefeDepartment of Radiology, Department of Neurology, Department of Pathology & Immunology, Department of Psychiatry, Division of Biostatistics, Washington University in St. Louis School of Medicine, Saint Louis, MO, USA.
Aylin DincerDepartment of Radiology, Department of Neurology, Department of Pathology & Immunology, Department of Psychiatry, Division of Biostatistics, Washington University in St. Louis School of Medicine, Saint Louis, MO, USA.
Beau M AncesDepartment of Radiology, Department of Neurology, Department of Pathology & Immunology, Department of Psychiatry, Division of Biostatistics, Washington University in St. Louis School of Medicine, Saint Louis, MO, USA.
Sarah B BermanAlzheimer Disease Research Center and Pittsburgh Institute for Neurodegenerative Diseases, University of Pittsburgh School of Medicine, 4-West Montefiore University Hospital, 200 Lothrop Street, Pittsburgh, PA, USA.
Adam M BrickmanDepartment of Neurology, Columbia University Medical Center, New York, NY, USA.
David M CashDementia Research Centre, UCL Queen Square Institute of Neurology, London, UK.
Jasmeer ChhatwalDepartment of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Carlos CruchagaDepartment of Radiology, Department of Neurology, Department of Pathology & Immunology, Department of Psychiatry, Division of Biostatistics, Washington University in St. Louis School of Medicine, Saint Louis, MO, USA.
Michael EwersInstitute for Stroke and Dementia Research, Klinikum der Universität München, Ludwig-Maximilians-Universität LMU, Munich, Germany.
Nick N FoxDepartment of Neurodegenerative Disease, Dementia Research Centre, UCL Institute of Neurology, London, UK.
Bernardino GhettiDepartment of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN, USA.
Alison GoateDepartment of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Neill R Graff-RadfordDepartment of Neuroscience, Mayo Clinic, Jacksonville, FL, USA; Department of Neurology, Mayo Clinic, Jacksonville, FL, USA.
Jason J HassenstabDepartment of Radiology, Department of Neurology, Department of Pathology & Immunology, Department of Psychiatry, Division of Biostatistics, Washington University in St. Louis School of Medicine, Saint Louis, MO, USA.
Russ HornbeckDepartment of Radiology, Department of Neurology, Department of Pathology & Immunology, Department of Psychiatry, Division of Biostatistics, Washington University in St. Louis School of Medicine, Saint Louis, MO, USA.
Clifford JackDepartment of Radiology, Mayo Clinic, Rochester, MN, USA.
Keith JohnsonDepartment of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Nelly Joseph-MathurinDepartment of Radiology, Department of Neurology, Department of Pathology & Immunology, Department of Psychiatry, Division of Biostatistics, Washington University in St. Louis School of Medicine, Saint Louis, MO, USA.
Celeste M KarchDepartment of Radiology, Department of Neurology, Department of Pathology & Immunology, Department of Psychiatry, Division of Biostatistics, Washington University in St. Louis School of Medicine, Saint Louis, MO, USA.
Robert A KoeppeDepartment of Radiology, University of Michigan, Ann Arbor, USA.
Athene K W LeeDepartment of Psychiatry and Human Behavior, Butler Hospital, Warren Alpert Medical School, Brown University, Providence, RI, USA.
Johannes LevinGerman Center for Neurodegenerative Diseases (DZNE), Munich, Germany; Department of Neurology, Klinikum der Universität München, Ludwig-Maximilians-Universität München, Munich, Germany; Munich Cluster for Systems Neurology (SyNergy), Germany.
Colin MastersThe Florey Institute, University of Melbourne, Parkville, VIC, Australia.
Eric McDadeDepartment of Radiology, Department of Neurology, Department of Pathology & Immunology, Department of Psychiatry, Division of Biostatistics, Washington University in St. Louis School of Medicine, Saint Louis, MO, USA.
Richard J PerrinDepartment of Radiology, Department of Neurology, Department of Pathology & Immunology, Department of Psychiatry, Division of Biostatistics, Washington University in St. Louis School of Medicine, Saint Louis, MO, USA.
Christopher C RoweDepartment of Molecular Imaging & Therapy, Austin Health, Melbourne, Australia.
Stephen SallowayDepartment of Neurology, Butler Hospital, Warren Alpert Medical School, Brown University, Providence, RI, USA.
Andrew J SaykinDepartment of Neurology, Department of Radiology, Indiana University School of Medicine, Indianapolis, IN, USA.
Reisa SperlingDepartment of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Yi SuBanner Alzheimer's Institute, Phoenix, AZ, USA.
Victor L VillemagneDepartment of Molecular Imaging & Therapy, Austin Health, Melbourne, Australia.
Jonathan VögleinGerman Center for Neurodegenerative Diseases (DZNE), Munich, Germany; Department of Neurology, Klinikum der Universität München, Ludwig-Maximilians-Universität München, Munich, Germany; Munich Cluster for Systems Neurology (SyNergy), Germany.
Michael WeinerDepartments of Psychiatry, Radiology, Medicine, and Neurology, University of California at San Francisco, San Francisco, CA, USA.
Chengjie XiongDepartment of Radiology, Department of Neurology, Department of Pathology & Immunology, Department of Psychiatry, Division of Biostatistics, Washington University in St. Louis School of Medicine, Saint Louis, MO, USA.
Anne M FaganDepartment of Radiology, Department of Neurology, Department of Pathology & Immunology, Department of Psychiatry, Division of Biostatistics, Washington University in St. Louis School of Medicine, Saint Louis, MO, USA.
John C MorrisDepartment of Radiology, Department of Neurology, Department of Pathology & Immunology, Department of Psychiatry, Division of Biostatistics, Washington University in St. Louis School of Medicine, Saint Louis, MO, USA.
Randall J BatemanDepartment of Radiology, Department of Neurology, Department of Pathology & Immunology, Department of Psychiatry, Division of Biostatistics, Washington University in St. Louis School of Medicine, Saint Louis, MO, USA.
Tammie L S BenzingerDepartment of Radiology, Department of Neurology, Department of Pathology & Immunology, Department of Psychiatry, Division of Biostatistics, Washington University in St. Louis School of Medicine, Saint Louis, MO, USA.
Mathias JuckerDZNE-German Center for Neurodegenerative Diseases, D-72076 Tübingen, Germany; Department of Cellular Neurology, Hertie Institute for Clinical Brain Research, University of Tübingen, D-72076 Tübingen, Germany.
Brian A GordonDepartment of Radiology, Department of Neurology, Department of Pathology & Immunology, Department of Psychiatry, Division of Biostatistics, Washington University in St. Louis School of Medicine, Saint Louis, MO, USA. Electronic address: bagordon@wustl.edu.
Dominantly Inherited Alzheimer Network
Washington University in St. Louis · USGerman Center for Neurodegenerative Diseases · DEHarvard University · USAustin Health · AUBrown University · USIndiana University School of MedicineUK Dementia Research Institute · GBBanner Alzheimer’s InstituteColumbia University Irving Medical Center · USIcahn School of Medicine at Mount Sinai · USJacksonville College · USLudwig-Maximilians-Universität München · DEMayo Clinic in Arizona · USThe University of Melbourne · AUUniversity of Basel · CHUniversity of California, San Francisco · USUniversity of Michigan · USUniversity of Pittsburgh · US
Funding
Imaging CoreU19AG032438 · NIA · WASHINGTON UNIVERSITY · PI BATEMAN, RANDALL J · 2010 to 2025
$53.9MResearch Education ComponentP30AG019610 · NIA · SUN HEALTH RESEARCH INSTITUTE · PI ALEXANDER, GENE E · 2001 to 2020
$32.5MDominantly Inherited Alzheimer NetworkUF1AG032438 · NIA · WASHINGTON UNIVERSITY · PI BATEMAN, RANDALL J · 2014 to 2017
$21.6MPET, APOE & the Preclinical Course of Alzheimer's DiseaseR01AG031581 · NIA · BANNER ALZHEIMER'S INSTITUTE · PI CASELLI, RICHARD J., REIMAN, ERIC MICHAEL · 2008 to 2018
$16.6MNeuroimaging Markers of Emerging Dysfunction In Preclinical Alzheimer DiseaseK01AG053474 · NIA · WASHINGTON UNIVERSITY · PI GORDON, BRIAN ANDREW · 2017 to 2021
$623kDepartment of HealthMedical Research Council MR/009076/1Medical Research Council MR/L023784/1NIA NIH HHS K01 AG053474NIA NIH HHS P30 AG019610NIA NIH HHS R01 AG031581NIA NIH HHS U19 AG032438NIA NIH HHS UF1 AG032438
Abstract
Neurofilament light chain (NfL) is a protein that is selectively expressed in neurons. Increased levels of NfL measured in either cerebrospinal fluid or blood is thought to be a biomarker of neuronal damage in neurodegenerative diseases. However, there have been limited investigations relating NfL to the concurrent measures of white matter (WM) decline that it should reflect. White matter damage is a common feature of Alzheimer's disease. We hypothesized that serum levels of NfL would associate with WM lesion volume and diffusion tensor imaging (DTI) metrics cross-sectionally in 117 autosomal dominant mutation carriers (MC) compared to 84 non-carrier (NC) familial controls as well as in a subset (N = 41) of MC with longitudinal NfL and MRI data. In MC, elevated cross-sectional NfL was positively associated with WM hyperintensity lesion volume, mean diffusivity, radial diffusivity, and axial diffusivity and negatively with fractional anisotropy. Greater change in NfL levels in MC was associated with larger changes in fractional anisotropy, mean diffusivity, and radial diffusivity, all indicative of reduced WM integrity. There were no relationships with NfL in NC. Our results demonstrate that blood-based NfL levels reflect WM integrity and supports the view that blood levels of NfL are predictive of WM damage in the brain. This is a critical result in improving the interpretability of NfL as a marker of brain integrity, and for validating this emerging biomarker for future use in clinical and research settings across multiple neurodegenerative diseases.
Indexed as
AdultAlzheimer DiseaseBiomarkersBrainDiffusion Tensor ImagingFemaleHumansMaleMiddle AgedWhite MatterBiomarkersAlzheimer's diseaseBlood-based biomarkersNeurodegenerationNeurofilamentNeuroimagingWhite matter
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