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Nat Med. 2019 Feb;25(2):277-283. doi: 10.1038/s41591-018-0304-3. Epub 2019 Jan 21.

Serum neurofilament dynamics predicts neurodegeneration and clinical progression in presymptomatic Alzheimer's disease.

Author information

1
German Center for Neurodegenerative Diseases (DZNE), Tübingen, Germany.
2
Department of Cellular Neurology, Hertie Institute for Clinical Brain Research, and Department of Psychiatry and Psychotherapy, University of Tübingen, Tübingen, Germany.
3
Department of Neurology, Department of Radiology, and Division of Biostatistics, Washington University School of Medicine, St. Louis, MO, USA.
4
Neurologic Clinic and Policlinic, Departments of Medicine, Biomedicine and Clinical Research, University Hospital Basel, University of Basel, Basel, Switzerland.
5
German Center for Neurodegenerative Diseases (DZNE), Munich, Germany.
6
Department of Neurology, Ludwig-Maximilians-Universität München, Munich, Germany.
7
Neurodegeneration Division, The Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, Victoria, Australia.
8
School of Medical Health and Sciences, Edith Cowan University, Joondalup, Western Australia, Australia.
9
Department of Biomedical Sciences, Macquarie University, Sydney, New South Wales, Australia.
10
Neuroscience Research Australia, Randwick, New South Wales, Australia.
11
School of Medical Sciences, University of New South Wales, Sydney, New South Wales, Australia.
12
Dementia Research Centre, Department of Neurodegeneration, Queen Square Institute of Neurology, University College London, London, UK.
13
Department of Neurology, Mayo Clinic Jacksonville, Jacksonville, FL, USA.
14
Warren Alpert Medical School of Brown University, Providence, RI, USA.
15
Indiana Alzheimer Disease Center and Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN, USA.
16
Department of Neurology, Keck School of Medicine at USC, Los Angeles, CA, USA.
17
Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Department of Neurology, Columbia University Medical Center, New York, NY, USA.
18
Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
19
Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
20
German Center for Neurodegenerative Diseases (DZNE), Tübingen, Germany. mathias.jucker@uni-tuebingen.de.
21
Department of Cellular Neurology, Hertie Institute for Clinical Brain Research, and Department of Psychiatry and Psychotherapy, University of Tübingen, Tübingen, Germany. mathias.jucker@uni-tuebingen.de.

Abstract

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.

PMID:
30664784
PMCID:
PMC6367005
[Available on 2020-02-01]
DOI:
10.1038/s41591-018-0304-3
[Indexed for MEDLINE]

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