Neurobiology of Disease (Aug 2020)
Serum neurofilament light chain levels are associated with white matter integrity in autosomal dominant Alzheimer's disease
- Stephanie A. Schultz,
- Jeremy F. Strain,
- Adedamola Adedokun,
- Qing Wang,
- Oliver Preische,
- Jens Kuhle,
- Shaney Flores,
- Sarah Keefe,
- Aylin Dincer,
- Beau M. Ances,
- Sarah B. Berman,
- Adam M. Brickman,
- David M. Cash,
- Jasmeer Chhatwal,
- Carlos Cruchaga,
- Michael Ewers,
- Nick N. Fox,
- Bernardino Ghetti,
- Alison Goate,
- Neill R. Graff-Radford,
- Jason J. Hassenstab,
- Russ Hornbeck,
- Clifford Jack, Jr,
- Keith Johnson,
- Nelly Joseph-Mathurin,
- Celeste M. Karch,
- Robert A. Koeppe,
- Athene K.W. Lee,
- Johannes Levin,
- Colin Masters,
- Eric McDade,
- Richard J. Perrin,
- Christopher C. Rowe,
- Stephen Salloway,
- Andrew J. Saykin,
- Reisa Sperling,
- Yi Su,
- Victor L. Villemagne,
- Jonathan Vöglein,
- Michael Weiner,
- Chengjie Xiong,
- Anne M. Fagan,
- John C. Morris,
- Randall J. Bateman,
- Tammie L.S. Benzinger,
- Mathias Jucker,
- Brian A. Gordon
Affiliations
- Stephanie A. Schultz
- Department 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. Strain
- Department 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 Adedokun
- Department 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 Wang
- Department 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 Preische
- DZNE-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 Kuhle
- Neurologic Clinic and Policlinic, Departments of Medicine, Biomedicine and Clinical Research, University Hospital Basel, University of Basel, CH-4031 Basel, Switzerland
- Shaney Flores
- Department 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 Keefe
- Department 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 Dincer
- Department 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. Ances
- Department 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. Berman
- Alzheimer 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. Brickman
- Department of Neurology, Columbia University Medical Center, New York, NY, USA
- David M. Cash
- Dementia Research Centre, UCL Queen Square Institute of Neurology, London, UK
- Jasmeer Chhatwal
- Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
- Carlos Cruchaga
- Department 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 Ewers
- Institute for Stroke and Dementia Research, Klinikum der Universität München, Ludwig-Maximilians-Universität LMU, Munich, Germany
- Nick N. Fox
- Department of Neurodegenerative Disease, Dementia Research Centre, UCL Institute of Neurology, London, UK
- Bernardino Ghetti
- Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN, USA
- Alison Goate
- Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, USA
- Neill R. Graff-Radford
- Department of Neuroscience, Mayo Clinic, Jacksonville, FL, USA; Department of Neurology, Mayo Clinic, Jacksonville, FL, USA
- Jason J. Hassenstab
- Department 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 Hornbeck
- Department 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 Jack, Jr
- Department of Radiology, Mayo Clinic, Rochester, MN, USA
- Keith Johnson
- Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
- Nelly Joseph-Mathurin
- Department 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. Karch
- Department 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. Koeppe
- Department of Radiology, University of Michigan, Ann Arbor, USA
- Athene K.W. Lee
- Department of Psychiatry and Human Behavior, Butler Hospital, Warren Alpert Medical School, Brown University, Providence, RI, USA
- Johannes Levin
- German 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 Masters
- The Florey Institute, University of Melbourne, Parkville, VIC, Australia
- Eric McDade
- Department 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. Perrin
- Department 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. Rowe
- Department of Molecular Imaging & Therapy, Austin Health, Melbourne, Australia
- Stephen Salloway
- Department of Neurology, Butler Hospital, Warren Alpert Medical School, Brown University, Providence, RI, USA
- Andrew J. Saykin
- Department of Neurology, Department of Radiology, Indiana University School of Medicine, Indianapolis, IN, USA
- Reisa Sperling
- Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
- Yi Su
- Banner Alzheimer's Institute, Phoenix, AZ, USA
- Victor L. Villemagne
- Department of Molecular Imaging & Therapy, Austin Health, Melbourne, Australia
- Jonathan Vöglein
- German 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 Weiner
- Departments of Psychiatry, Radiology, Medicine, and Neurology, University of California at San Francisco, San Francisco, CA, USA
- Chengjie Xiong
- Department 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. Fagan
- Department 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. Morris
- Department 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. Bateman
- Department 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. Benzinger
- Department 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 Jucker
- DZNE-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. Gordon
- Department 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; Corresponding author at: Washington University School of Medicine, 660 South Euclid, Campus Box 8225, St. Louis, MO 63110, USA.
- Journal volume & issue
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Vol. 142
p. 104960
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.
