Longitudinal, and thus repeated sampling of cerebrospinal fluid (CSF) from a single animal, combined with repeated measurements of biomarkers, offers a highly translational approach for analyzing progressive pathological changes while minimizing the number of needed animals.
The CSF composition reflects biological changes inside the central nervous system and can thus be used to observe pathological states of the brain or spinal cord without invasively accessing these tissues. Its analysis has therefore been used for years to detect CNS pathology. Neurofilaments constitute the backbone of the neuronal cytoskeleton and neurofilament light chain (NF-L) is by now an indispensable biomarker for neurodegenerative processes when measured in blood plasma or CSF of patients or mouse models of neurodegenerative diseases.
For the analysis of NF-L levels, Scantox Neuro uses the NF-Light® ELISA by UmanDiagnostics, an assay well-described for the analysis of human clinical samples as well as murine samples.
Longitudinal measurements of NF-L in 4L/PS-NA mice, a model of Gaucher disease, show progressively increasing levels of NF-L in 4L/PS-NA mice compared to wild type littermates. Significant differences in NF-L levels can be observed starting at an age of 12 weeks (Figure 1).
Figure 1: Longitudinal quantification of NF-L levels in the CSF of 4L/PS-NA mice and wild type littermates. CSF samples were repeatedly taken from the same animals at the age of 4, 12, and 17 weeks. Two-way ANOVA followed by Sidak’s multiple comparison post hoc test. n=13 per group. Mean ± SEM; ***/###p<0.001.
Longitudinal measurements of NF-L in NPC1-/- mice, a model of Niemann-Pick disease, also shows progressively increasing levels of NF-L in NPC1-/- mice compared to wild type littermates. Significant differences in NF-L levels can be observed starting as early as 5 weeks of age (Figure 2).
Figure 2: Quantification of NF-L levels in the CSF of NPC1-/- mice and wild type littermates. CSF samples were repeatedly taken from the same animals at the age of 5, 9, and 10 weeks. Two-way ANOVA followed by Sidak’s multiple comparison post hoc test. n=7-8 per group. Mean ± SEM; **p<0.01; ***/###p<0,001.
NF-L measurements obtained from high-quality in vivo sampled CSF, result in robust data about disease progression in 4L-PS/NA and NPC1-/- mice that model Gaucher and Niemann-Pick disease.
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