Journal Article

DZNE-2020-05060

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Neurofilament Light Chain in Blood and CSF as Marker of Disease Progression in Mouse Models and in Neurodegenerative Diseases.

Bacioglu, M. (First author)DZNE* ; Maia, L. F.DZNE* ; Preische, O.DZNE* ; Schelle, J.DZNE* ; Apel, A.DZNE* ; Kaeser, S. A.DZNE* ; Schweighauser, M.DZNE* ; Eninger, T.DZNE* ; Lambert, M.DZNE* ; Pilotto, A.DZNE* ; Shimshek, D. R. ; Neumann, U. ; Kahle, P. J.DZNE* ; Staufenbiel, M.DZNE* ; Neumann, M.DZNE* ; Maetzler, W.DZNE* ; Kuhle, J. (Corresponding author) ; Jucker, M. (Last author)DZNE*

2016
Elsevier New York, NY

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Please use a persistent id in citations: doi:10.1016/j.neuron.2016.05.018

Abstract: A majority of current disease-modifying therapeutic approaches for age-related neurodegenerative diseases target their characteristic proteopathic lesions (α-synuclein, Tau, Aβ). To monitor such treatments, fluid biomarkers reflecting the underlying disease process are crucial. We found robust increases of neurofilament light chain (NfL) in CSF and blood in murine models of α-synucleinopathies, tauopathy, and β-amyloidosis. Blood and CSF NfL levels were strongly correlated, and NfL increases coincided with the onset and progression of the corresponding proteopathic lesions in brain. Experimental induction of α-synuclein lesions increased CSF and blood NfL levels, while blocking Aβ lesions attenuated the NfL increase. Consistently, we also found NfL increases in CSF and blood of human α-synucleinopathies, tauopathies, and Alzheimer's disease. Our results suggest that CSF and particularly blood NfL can serve as a reliable and easily accessible biomarker to monitor disease progression and treatment response in mouse models and potentially in human proteopathic neurodegenerative diseases.

Keyword(s): Animals (MeSH) ; Axons: metabolism (MeSH) ; Biomarkers: blood (MeSH) ; Biomarkers: cerebrospinal fluid (MeSH) ; Brain: metabolism (MeSH) ; Brain: pathology (MeSH) ; Disease Progression (MeSH) ; Intermediate Filaments: metabolism (MeSH) ; Mice, Inbred C57BL (MeSH) ; Mice, Transgenic (MeSH) ; Neurodegenerative Diseases: diagnosis (MeSH) ; Neurodegenerative Diseases: metabolism (MeSH) ; Neurodegenerative Diseases: pathology (MeSH) ; Neurofilament Proteins: blood (MeSH) ; Neurofilament Proteins: cerebrospinal fluid (MeSH) ; alpha-Synuclein: metabolism (MeSH) ; Biomarkers ; Neurofilament Proteins ; alpha-Synuclein

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Contributing Institute(s):

1. Cell Biology of Neurological Diseases (AG Jucker)
2. Functional Neurogenetics (AG Kahle)
3. Ext UKT TREND Studie (Ext UKT-Trend)
4. Molecular Neuropathology of Neurodegenerative Diseases (AG Neumann)
5. Functional Neurogeriatrics (AG Maetzler)

Research Program(s):

1. 342 - Disease Mechanisms and Model Systems (POF3-342) (POF3-342)
2. 345 - Population Studies and Genetics (POF3-345) (POF3-345)
3. 344 - Clinical and Health Care Research (POF3-344) (POF3-344)

Appears in the scientific report 2016

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Database coverage:
; BIOSIS Previews ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; Ebsco Academic Search ; IF >= 10 ; JCR ; NCBI Molecular Biology Database ; Nationallizenz ; SCOPUS ; Science Citation Index ; Science Citation Index Expanded ; Web of Science Core Collection

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