Biomarkers are an emerging area of focus in neurodegenerative diseases. This new scrutiny has arisen because biomarkers may provide an important link between preclinical disease models and the evaluation of disease progression in patients.
One of these biomarkers, neurofilament light chain (NF-L), a neuronal cytoplasmic protein, is increased in a variety of neuronal diseases due to axonal damage. In particular, an increase of NF-L levels has recently been found in ALS (Amyotrophic Lateral Sclerosis) patients (Gaetani et. al, 2018).
To further explore this finding, QPS researched NF-L levels in the low copy transgenic mouse model, SOD1-G93A. The results added to our knowledge, showing increased plasma NF-L levels at just 24 weeks of age. This result reached significance at 27 weeks (Fig. 1).
To further test this theory, QPS ran similar experiments in the familial Alzheimer’s disease mouse model, 5xFAD. The results were similar, showing that an increase in plasma NF-L levels can be observed at 6 months of age (Fig. 2A). Taking another look at the same model, this time examining cerebrospinal fluid (CSF), strongly elevated CSF NF-L levels can be detected in 9-month-old 5xFAD mice (Fig. 2B).
This exciting research paves the way for closer scrutiny of NF-L levels in the evaluation of disease progression in neurodegenerative diseases.
Figure 1: Quantification of neurofilament light chain in plasma of low copy SOD1-G93A mice. NF-L levels in pg/mL in the plasma of 24, 27 and 30 week old SOD1-G93A mice compared to non-transgenic littermates (ntg). Two-way ANOVA with Tukey’s post hoc test. Mean + SEM. *p<0.05; ***p<0.001. *compared to ntg; # differences between age groups.
Figure 2: Quantification of neurofilament light chain in plasma and CSF of 5xFAD mice. A: NF-L levels in pg/mL in the plasma of 3, 6, 9 and 12 month old 5xFAD mice compared to non-transgenic littermates (ntg). Two-way ANOVA with Bonferroni‘s post hoc test. B: NF-L levels in pg/mL in the CSF of 9 months old 5xFAD mice compared to ntg. Unpaired t-test. A and B: Mean + SEM. *p<0.05; **p<0.01; ***p<0.001.
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