Phosphorylation and compactness of neurofilaments in multiple sclerosis: Indicators of axonal pathology
2008

Neurofilament Phosphorylation in Multiple Sclerosis

Sample size: 77 publication Evidence: moderate

Author Information

Author(s): Petzold Axel, Gveric Djordje, Groves Mike, Schmierer Klaus, Grant Donna, Chapman Miles, Keir Geoffrey, Cuzner Louise, Thompson Edward J.

Primary Institution: Institute of Neurology, Queen Square, London, UK

Hypothesis

This study investigated whether neurofilament (NfH) phosphorylation would relate to the dynamics of axonal pathology in multiple sclerosis (MS).

Conclusion

The findings suggest that a less organized axoskeleton or impaired axonal transport may represent an early sign of axonal pathology within the normal appearing white matter in MS.

Supporting Evidence

  • In control tissue, a rostro-caudal gradient of NfH indicated an increase in axonal density from the brain gray matter towards the spinal cord.
  • The highest levels of phosphorylated NfH were found in acute lesions of brain and spinal cord.
  • Dephosphorylated NfH was higher but less densely packed in MS white matter axons compared to control tissue.
  • Significant differences in tissue levels were found in normal-appearing white matter, acute lesions, and chronic lesions for phosphorylated NfH.

Takeaway

This study looked at how a protein called neurofilament changes in people with multiple sclerosis, showing that these changes might indicate early signs of nerve damage.

Methodology

NfH phosphoforms were quantified by ELISA from microdissected samples of control and MS brain and spinal cord, and individual axons were analyzed by electron microscopy.

Potential Biases

The study may have bias due to the selection of patients only from a specific phase of MS.

Limitations

The study only included patients with secondary progressive MS and did not assess early stages of the disease.

Participant Demographics

Patients with secondary MS according to the Poser criteria and age-matched controls.

Statistical Information

P-Value

<0.05

Statistical Significance

p<0.05

Digital Object Identifier (DOI)

10.1016/j.expneurol.2008.06.008

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