Neurofilament Light Chain in Blood and CSF as Marker of Disease Progression in Mouse Models and in Neurodegenerative Diseases.
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.
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.
Mehtap
M
Bacioglu
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.
Luis F
LF
Maia
German Center for Neurodegenerative Diseases (DZNE), Tuebingen, D-72076 Tuebingen, Germany; Department of Psychiatry and Psychotherapy, University of Tuebingen, D-72076 Tuebingen, Germany.
Oliver
O
Preische
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.
Juliane
J
Schelle
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.
Anja
A
Apel
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.
Stephan A
SA
Kaeser
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.
Manuel
M
Schweighauser
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.
Timo
T
Eninger
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.
Marius
M
Lambert
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.
Andrea
A
Pilotto
Novartis Institutes for BioMedical Research, Novartis Pharma AG, CH-4002 Basel, Switzerland.
Derya R
DR
Shimshek
Novartis Institutes for BioMedical Research, Novartis Pharma AG, CH-4002 Basel, Switzerland.
Ulf
U
Neumann
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.
Philipp J
PJ
Kahle
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.
Matthias
M
Staufenbiel
German Center for Neurodegenerative Diseases (DZNE), Tuebingen, D-72076 Tuebingen, Germany; Department of Neuropathology, University of Tuebingen, D-72076 Tuebingen, Germany.
Manuela
M
Neumann
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.
Walter
W
Maetzler
Neurology, Departments of Medicine, Biomedicine, and Clinical Research, University Hospital Basel, CH-4031 Basel, Switzerland. Electronic address: jens.kuhle@usb.ch.
Jens
J
Kuhle
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.
Mathias
M
Jucker
D000818:Animals; D001369:Axons / Q000378:metabolism; D015415:Biomarkers / Q000097:blood / Q000134:cerebrospinal fluid; D001921:Brain / Q000378:metabolism / Q000473:pathology; D018450:Disease Progression; D007382:Intermediate Filaments / Q000378:metabolism*; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D019636:Neurodegenerative Diseases / Q000175:diagnosis / Q000378:metabolism* / Q000473:pathology; D016900:Neurofilament Proteins / Q000097:blood* / Q000134:cerebrospinal fluid*; D051844:alpha-Synuclein / Q000378:metabolism
D015415:Biomarkers; D016900:Neurofilament Proteins; D051844:alpha-Synuclein