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J Neurol Neurosurg Psychiatry 81:e62 doi:10.1136/jnnp.2010.226340.179
  • ABN Abstracts

PONM06 Plasma neurofilament heavy chain levels as a disease biomarker in the SOD1 mouse model of amyotrophic lateral sclerosis

  1. L Greensmith
  1. UCL Institute of Neurology, London, UK
  1. Correspondence to clu{at}ion.ucl.ac.uk

Abstract

One of the pathological hallmarks of Amyotrophic Lateral Sclerosis (ALS) is the presence of cytoplasmic inclusions with neurofilament immunoreactivity, suggesting a dysfunction in protein quality control in ALS. In this study, using the SOD1G93A mouse model of ALS, we examined whether plasma neurofilament levels may be a possible biomarker for ALS. Plasma levels of neurofilament heavy chain (NfH) were measured in SOD1G93A mice and their wild type (WT) littermates at various stages of disease progression from presymptomatic to end-stage, accompanied by functional assessment of grip strength and body weight. We used a sandwich ELISA developed in house to detect hyperphosphorylated and variably-phosphorylated NfH, NfH-SMI34 and NfH-SMI35, respectively. There was a significant difference in plasma NfH levels in WT and SOD1G93A mice, although NfH-SMI34 levels appeared to be a better marker for differentiating diseased and healthy mice. Furthermore, both NfH-SMI34 and NfH-SMI35 levels increased significantly as disease progressed in SOD1G93A mice. We also found a strong negative correlation between grip strength and NfH levels in SOD1G93A mice. Our results show that plasma NfH levels are a reliable biomarker of disease progression in the SOD1G93A mouse model of ALS. The possibility that plasma NfH levels may also be a biomarker in ALS patients is currently under investigation.

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