Affordable Access

deepdyve-link
Publisher Website

Serum neurofilament light chain levels are associated with white matter integrity in autosomal dominant Alzheimer's disease.

Authors
  • Schultz, Stephanie A1
  • Strain, Jeremy F1
  • Adedokun, Adedamola1
  • Wang, Qing1
  • Preische, Oliver2
  • Kuhle, Jens3
  • Flores, Shaney1
  • Keefe, Sarah1
  • Dincer, Aylin1
  • Ances, Beau M1
  • Berman, Sarah B4
  • Brickman, Adam M5
  • Cash, David M6
  • Chhatwal, Jasmeer7
  • Cruchaga, Carlos1
  • Ewers, Michael8
  • Fox, Nick N9
  • Ghetti, Bernardino10
  • Goate, Alison11
  • Graff-Radford, Neill R12
  • And 27 more
  • 1 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.
  • 2 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. , (Germany)
  • 3 Neurologic Clinic and Policlinic, Departments of Medicine, Biomedicine and Clinical Research, University Hospital Basel, University of Basel, CH-4031 Basel, Switzerland. , (Switzerland)
  • 4 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.
  • 5 Department of Neurology, Columbia University Medical Center, New York, NY, USA.
  • 6 Dementia Research Centre, UCL Queen Square Institute of Neurology, London, UK.
  • 7 Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
  • 8 Institute for Stroke and Dementia Research, Klinikum der Universität München, Ludwig-Maximilians-Universität LMU, Munich, Germany. , (Germany)
  • 9 Department of Neurodegenerative Disease, Dementia Research Centre, UCL Institute of Neurology, London, UK.
  • 10 Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN, USA. , (India)
  • 11 Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • 12 Department of Neuroscience, Mayo Clinic, Jacksonville, FL, USA; Department of Neurology, Mayo Clinic, Jacksonville, FL, USA.
  • 13 Department of Radiology, Mayo Clinic, Rochester, MN, USA.
  • 14 Department of Radiology, University of Michigan, Ann Arbor, USA.
  • 15 Department of Psychiatry and Human Behavior, Butler Hospital, Warren Alpert Medical School, Brown University, Providence, RI, USA.
  • 16 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. , (Germany)
  • 17 The Florey Institute, University of Melbourne, Parkville, VIC, Australia. , (Australia)
  • 18 Department of Molecular Imaging & Therapy, Austin Health, Melbourne, Australia. , (Australia)
  • 19 Department of Neurology, Butler Hospital, Warren Alpert Medical School, Brown University, Providence, RI, USA.
  • 20 Department of Neurology, Department of Radiology, Indiana University School of Medicine, Indianapolis, IN, USA. , (India)
  • 21 Banner Alzheimer's Institute, Phoenix, AZ, USA.
  • 22 Departments of Psychiatry, Radiology, Medicine, and Neurology, University of California at San Francisco, San Francisco, CA, USA.
  • 23 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. Electronic address: [email protected]
Type
Published Article
Journal
Neurobiology of Disease
Publisher
Elsevier
Publication Date
Aug 01, 2020
Volume
142
Pages
104960–104960
Identifiers
DOI: 10.1016/j.nbd.2020.104960
PMID: 32522711
Source
Medline
Keywords
Language
English
License
Unknown

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. Copyright © 2020. Published by Elsevier Inc.

Report this publication

Statistics

Seen <100 times