Serum neurofilament dynamics predicts neurodegeneration and clinical progression in presymptomatic Alzheimer's disease.
- Preische O German Center for Neurodegenerative Diseases (DZNE), Tübingen, Germany.
- Schultz SA Department of Neurology, Department of Radiology, and Division of Biostatistics, Washington University School of Medicine, St. Louis, MO, USA.
- Apel A German Center for Neurodegenerative Diseases (DZNE), Tübingen, Germany.
- Kuhle J Neurologic Clinic and Policlinic, Departments of Medicine, Biomedicine and Clinical Research, University Hospital Basel, University of Basel, Basel, Switzerland.
- Kaeser SA German Center for Neurodegenerative Diseases (DZNE), Tübingen, Germany.
- Barro C Neurologic Clinic and Policlinic, Departments of Medicine, Biomedicine and Clinical Research, University Hospital Basel, University of Basel, Basel, Switzerland.
- Gräber S German Center for Neurodegenerative Diseases (DZNE), Tübingen, Germany.
- Kuder-Buletta E German Center for Neurodegenerative Diseases (DZNE), Tübingen, Germany.
- LaFougere C German Center for Neurodegenerative Diseases (DZNE), Tübingen, Germany.
- Laske C German Center for Neurodegenerative Diseases (DZNE), Tübingen, Germany.
- Vöglein J German Center for Neurodegenerative Diseases (DZNE), Munich, Germany.
- Levin J German Center for Neurodegenerative Diseases (DZNE), Munich, Germany.
- Masters CL Neurodegeneration Division, The Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, Victoria, Australia.
- Martins R School of Medical Health and Sciences, Edith Cowan University, Joondalup, Western Australia, Australia.
- Schofield PR Neuroscience Research Australia, Randwick, New South Wales, Australia.
- Rossor MN Dementia Research Centre, Department of Neurodegeneration, Queen Square Institute of Neurology, University College London, London, UK.
- Graff-Radford NR Department of Neurology, Mayo Clinic Jacksonville, Jacksonville, FL, USA.
- Salloway S Warren Alpert Medical School of Brown University, Providence, RI, USA.
- Ghetti B Indiana Alzheimer Disease Center and Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN, USA.
- Ringman JM Department of Neurology, Keck School of Medicine at USC, Los Angeles, CA, USA.
- Noble JM Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Department of Neurology, Columbia University Medical Center, New York, NY, USA.
- Chhatwal J Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
- Goate AM Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
- Benzinger TLS Department of Neurology, Department of Radiology, and Division of Biostatistics, Washington University School of Medicine, St. Louis, MO, USA.
- Morris JC Department of Neurology, Department of Radiology, and Division of Biostatistics, Washington University School of Medicine, St. Louis, MO, USA.
- Bateman RJ Department of Neurology, Department of Radiology, and Division of Biostatistics, Washington University School of Medicine, St. Louis, MO, USA.
- Wang G Department of Neurology, Department of Radiology, and Division of Biostatistics, Washington University School of Medicine, St. Louis, MO, USA.
- Fagan AM Department of Neurology, Department of Radiology, and Division of Biostatistics, Washington University School of Medicine, St. Louis, MO, USA.
- McDade EM Department of Neurology, Department of Radiology, and Division of Biostatistics, Washington University School of Medicine, St. Louis, MO, USA.
- Gordon BA Department of Neurology, Department of Radiology, and Division of Biostatistics, Washington University School of Medicine, St. Louis, MO, USA.
- Jucker M German Center for Neurodegenerative Diseases (DZNE), Tübingen, Germany. mathias.jucker@uni-tuebingen.de.
- 2019-01-22
Published in:
- Nature medicine. - 2019
English
Neurofilament light chain (NfL) is a promising fluid biomarker of disease progression for various cerebral proteopathies. Here we leverage the unique characteristics of the Dominantly Inherited Alzheimer Network and ultrasensitive immunoassay technology to demonstrate that NfL levels in the cerebrospinal fluid (n = 187) and serum (n = 405) are correlated with one another and are elevated at the presymptomatic stages of familial Alzheimer's disease. Longitudinal, within-person analysis of serum NfL dynamics (n = 196) confirmed this elevation and further revealed that the rate of change of serum NfL could discriminate mutation carriers from non-mutation carriers almost a decade earlier than cross-sectional absolute NfL levels (that is, 16.2 versus 6.8 years before the estimated symptom onset). Serum NfL rate of change peaked in participants converting from the presymptomatic to the symptomatic stage and was associated with cortical thinning assessed by magnetic resonance imaging, but less so with amyloid-β deposition or glucose metabolism (assessed by positron emission tomography). Serum NfL was predictive for both the rate of cortical thinning and cognitive changes assessed by the Mini-Mental State Examination and Logical Memory test. Thus, NfL dynamics in serum predict disease progression and brain neurodegeneration at the early presymptomatic stages of familial Alzheimer's disease, which supports its potential utility as a clinically useful biomarker.
- Language
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- English
- Open access status
- green
- Identifiers
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- DOI 10.1038/s41591-018-0304-3
- PMID 30664784
- Persistent URL
- https://sonar.ch/global/documents/270263
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