ArticleFrontiers in neuroscience2024
NfL concentration in CSF is a quantitative marker of the rate of neurodegeneration in aging and Huntington's disease: a semi-mechanistic model-based analysis.
Article in Frontiers in neuroscience, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed.
- Fluid and Imaging Biomarkers in Huntington's Disease.Current neurology and neuroscience reports · 2026Review
- The neuroimmune network in Alzheimer's and Parkinson's diseases: from mechanistic insights to biomarker-guided immunotherapies and clinical translation.Inflammopharmacology · 2026Review
- Evaluation of sNfL as a Biomarker for Paclitaxel-Induced Peripheral Neurotoxicity Through an Integrated PKPD Model.Pharmaceutical research · 2026Article
- Multiomics approach identifies SERPINB1 as candidate biomarker for spinocerebellar ataxia type 2.Scientific reports · 2025Article
- BA9 Transcriptomics in Huntington's Disease 80-Gene Signature and MIR219A2-Linked Targets.International journal of molecular sciences · 2025Article
- Advances in Huntington's Disease Biomarkers: A 10-Year Bibliometric Analysis and a Comprehensive Review.Biology · 2025Review
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Abstract
The concentrations of neurofilament light chain (NfL) in cerebrospinal fluid (CSF) and plasma have become key biomarkers of many neurodegenerative diseases, including Huntington's Disease (HD). However, the relationship between the dynamics of NfL concentrations in CSF and the time-course of neurodegeneration (whole brain atrophy) has not yet been described in a quantitative and mechanistic manner. Here, we present a novel semi-mechanistic model, which postulates that the amount of NfL entering the CSF corresponds to the amount of NfL released from damaged neurons, whose degeneration results in a decrease in brain volume. In mathematical terms, the model expresses the NfL concentration in CSF in terms of the NfL concentration in brain tissue, the rate of change of whole brain volume and the CSF flow rate. To test our model, we used a non-linear mixed effects approach to analyze NfL and brain volume data from the HD-CSF study, a 24-month prospective study of individuals with premanifest HD, manifest HD and healthy controls. The time-course of whole brain volume, obtained from MRI, was represented empirically by a 2nd order polynomial, from which its rate of change was computed. CSF flow rates in healthy and HD populations were taken from recent literature data. By estimating the NfL concentration in brain tissue, the model successfully described the time-course of the NfL concentration in CSF in both HD subjects and healthy controls. Furthermore, the model-derived estimate of NfL concentration in brain agreed well with recent direct experimental measurements. The consistency of our model with the NfL and brain volume data suggests that the NfL concentration in CSF reflects the rate, rather than the extent, of neurodegeneration and that the increase in NfL concentration over time is a measure of the accelerating rate of neurodegeneration associated with aging and HD. For HD subjects, the degree of acceleration was found to increase markedly with the number of CAG repeats on their HTT gene. The application of our semi-mechanistic NfL model to other neurodegenerative diseases is discussed.
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