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Neuron. 2016 Jul 6;91(1):56-66. doi: 10.1016/j.neuron.2016.05.018. Epub 2016 Jun 9.

Neurofilament Light Chain in Blood and CSF as Marker of Disease Progression in Mouse Models and in Neurodegenerative Diseases.

Author information

1
German Center for Neurodegenerative Diseases (DZNE), Tuebingen, D-72076 Tuebingen, Germany; Department of Cellular Neurology, Hertie Institute for Clinical Brain Research, University of Tuebingen, D-72076 Tuebingen, Germany; Graduate School of Cellular and Molecular Neuroscience, University of Tuebingen, D-72074 Tuebingen, Germany.
2
German Center for Neurodegenerative Diseases (DZNE), Tuebingen, D-72076 Tuebingen, Germany; Department of Cellular Neurology, Hertie Institute for Clinical Brain Research, University of Tuebingen, D-72076 Tuebingen, Germany; Department of Neurology, Hospital de Santo António-CHP, 4099-001 Porto, Portugal.
3
German Center for Neurodegenerative Diseases (DZNE), Tuebingen, D-72076 Tuebingen, Germany; Department of Psychiatry and Psychotherapy, University of Tuebingen, D-72076 Tuebingen, Germany.
4
German Center for Neurodegenerative Diseases (DZNE), Tuebingen, D-72076 Tuebingen, Germany; Department of Neurodegeneration, Hertie Institute for Clinical Brain Research, University of Tuebingen, D-72076 Tuebingen, Germany.
5
German Center for Neurodegenerative Diseases (DZNE), Tuebingen, D-72076 Tuebingen, Germany; Department of Cellular Neurology, Hertie Institute for Clinical Brain Research, University of Tuebingen, D-72076 Tuebingen, Germany.
6
Novartis Institutes for BioMedical Research, Novartis Pharma AG, CH-4002 Basel, Switzerland.
7
German Center for Neurodegenerative Diseases (DZNE), Tuebingen, D-72076 Tuebingen, Germany; Department of Neuropathology, University of Tuebingen, D-72076 Tuebingen, Germany.
8
Neurology, Departments of Medicine, Biomedicine, and Clinical Research, University Hospital Basel, CH-4031 Basel, Switzerland. Electronic address: jens.kuhle@usb.ch.
9
German Center for Neurodegenerative Diseases (DZNE), Tuebingen, D-72076 Tuebingen, Germany; Department of Cellular Neurology, Hertie Institute for Clinical Brain Research, University of Tuebingen, D-72076 Tuebingen, Germany. Electronic address: mathias.jucker@uni-tuebingen.de.

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.

PMID:
27292537
DOI:
10.1016/j.neuron.2016.05.018
[Indexed for MEDLINE]
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