Neurofilament Light Chain in Blood and CSF as Marker of Disease Progression in Mouse Models and in Neurodegenerative Diseases
Authors: Juliane Schelle
Luis F Maia
Mehtap Bacioglu
Manuel Schweighauser
Timo Eninger
Andrea Pilotto
Walter Maetzler
Ulf Neumann
Mathias Jucker
Stephan A Kaeser
Marius Lambert
Anja Apel
Manuela Neumann
Derya R Shimshek
Jens Kuhle
Philipp J Kahle
Oliver Preische
Matthias Staufenbiel
Journal: Neuron (2016)
Discipline: NEUROSCIENCE & BEHAVIOR
Keywords: neurodegenerative diseases; biomarkers; NfL; proteopathic lesions; CSF
Affiliations: 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., 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., German Center for Neurodegenerative Diseases (DZNE), Tuebingen, D-72076 Tuebingen, Germany; Department of Psychiatry and Psychotherapy, University of Tuebingen, D-72076 Tuebingen, Germany., 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., 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., Novartis Institutes for BioMedical Research, Novartis Pharma AG, CH-4002 Basel, Switzerland., German Center for Neurodegenerative Diseases (DZNE), Tuebingen, D-72076 Tuebingen, Germany; Department of Neuropathology, University of Tuebingen, D-72076 Tuebingen, Germany., Neurology, Departments of Medicine, Biomedicine, and Clinical Research, University Hospital Basel, CH-4031 Basel, Switzerland. Electronic address: ., 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: .

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. 

Retracted: No

PubPeer comments:
 Supplemental Fig. S4: More similar than expected ![file] , 
 This note was forwarded to me (Mathias Jucker) as the corresponding author Thank you very much for bringing this to our attention. We will immediately look into this. Obviously this is twice the same picture and we are very embarrassed for the mistake Mathias Jucker , 
 We checked the original files and images. The published P301S hippocampus image is different from the one in our original data folder. Thus, unintentionally we apparently placed the A53T hippocampus image twice. This is an embarrassing mistake. The correct images look very similar to each other (see below) which could explain why we mixed them when we put together the panel but it does not explain why we and all the co-authors missed this in the process of reviewing our paper. Thank you again for bringing this to our attention and we will bring this mixup to the attention of the journal. Mathias Jucker ![file] ,