NF-L in cerebrospinal fluid and serum is a biomarker of neuronal damage in an inducible mouse model of neurodegeneration
Open accessAbstract
Accumulation of neurofilaments (NFs), the major constituents of the neuronal cytoskeleton, is a distinctive feature of neurological diseases and several studies have shown that soluble NFs can be detected in the cerebrospinal fluid (CSF) of patients with neurological diseases, such as multiple sclerosis and frontotemporal dementia. Here we have used an inducible transgenic mouse model of neurodegeneration, CamKII-TetOp25 mice, to evaluate whether NF-L levels in CSF or blood can be used as a biochemical biomarker of neurodegeneration. Induction of p25 transgene brain expression led to increase in CSF and serum NF-L levels that correlated with ongoing neurodegeneration. Switching off p25 prevented further increases in both CSF and serum NF-L levels and concomitantly stopped the progression of neurodegeneration. The levels of CSF NF-L detected in p25 mice are about 4-fold higher than the CSF levels detected in patients with chronic neurodegenerative diseases, such as symptomatic FTD (bvFTD). In addition, our data indicate that the NF-L detected in CSF is most likely a cleaved form of NF-L. These results suggest that CSF and serum NF-L are of interest to be further explored as potential translational dynamic biomarkers of neurodegeneration or as pharmacodynamics biomarkers at least in preclinical animal studies.
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In mice and in several neurological conditions, including proteopathic neurodegenerative diseases, fluid NfL changes have been associated with brain damage and atrophy.
“Changes of NfL in bodily fluids have been linked to brain damage and brain atrophy in mouse models and multiple neurological disorders including proteopathic neurodegenerative diseases11,13–16.”
From Serum neurofilament dynamics predicts neurodegeneration and clinical progression in presymptomatic Alzheimer’s disease (2019) · cites this paper as [15]
The assay likely detects a short, stable ~10 kD fragment from the core domain of NfL.
“The antigen detected with the (ultrasensitive) immunoassay used in this study is presumably a short and stable fragment (~10 kD) of the core domain of NfL15,29.”
From Serum neurofilament dynamics predicts neurodegeneration and clinical progression in presymptomatic Alzheimer’s disease (2019) · cites this paper as [15]
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- Authors
- Brureau, A., Blanchard-Bregeon, V., Pech, C., Hamon, S., Chaillou, P., Guillemot, J.-C., Barneoud, P., Bertrand, P., Pradier, L., Rooney, T., & Schussler, N.
- Affiliations
- Sanofi (France) (FR)
- Corresponding author
- Schussler, Nathalie
- ORCID
- Pradier, Laurent
- Venue
- Neurobiology of Disease
- Publisher
- Elsevier BV
- Published
- 2017-08
- Volume
- 104
- Pages
- 73-84
- ISSN
- 0969-9961 (ISSN-L)
- OpenAlex
- W2604264617
- Cited by
- 62
- References
- 63
- Citations by year
- 2026: 8 · 2025: 1 · 2024: 8 · 2023: 5 · 2022: 15 · 2021: 8 · 2020: 4 · 2019: 8 · 2018: 4 · 2017: 1
- FWCI
- 2.49
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Neurobiology of Disease (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- HAL (submittedVersion, cc-by-nc-nd)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Sanofi
- Massachusetts Institute of Technology
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Skin and Cellular Biology Research
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- neurofilament light chain, cerebrospinal fluid biomarkers, serum biomarkers, neurodegeneration, neuronal injury, frontotemporal dementia, multiple sclerosis, dynamic biomarkers
- MeSH terms
- RNA Splicing Factors, Animals, Brain, Disease Models, Animal, Fluoresceins, Mice, Transgenic, Neurons, Phosphopyruvate Hydratase, Phosphotransferases, Neurofilament Proteins, Neurodegenerative Diseases, Green Fluorescent Proteins, Mice, Calcium-Calmodulin-Dependent Protein Kinase Type 2
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