Research: more evidence for neurofilaments as a marker for progression

EpubGray et al. Accumulation of cortical hyperphosphorylated neurofilaments as a marker of neurodegeneration in multiple sclerosis. Mult Scler. 2012 Jun 21.

Background: Axonal loss and grey matter neuronal injury are pathological processes that contribute to disease progression in MS. Axon damage has been associated with changes in the phosphorylation state (phosphate groups) of neurofilaments and the presence of axonal spheroids (ball at the end of axons when they are transected). Perikaryal accumulation of abnormally phosphorylated neurofilament proteins has been reported in some neurodegenerative diseases.

Objectives: The objective of this article is to determine whether abnormally phosphorylated neurofilament accumulates in neuronal perikarya in demyelinated MS cortex.

Methods: We used an antibody to hyperphosphorylated neurofilament-H (SMI-34) to assess the level and distribution of this antigen in paraffin sections of cerebral cortex from cases of neuropathologically confirmed MS and controls. We also examined the relationship of neurofilament phosphorylation to cortical demyelination.

Results: The number of SMI-34-positive neuronal somata was significantly higher in the MS cortex than the control cortex. As a proportion of the total number of neurons present (i.e. taking account of neuronal loss), the proportion of SMI-34-positive neurons was also significantly higher in the demyelinated and non-demyelinated MS cortex than the control cortex.

Conclusions: MS is associated with the widespread accumulation of hyperphosphorylated neurofilament protein in neuronal somata, with the most marked accumulation in regions of cortical demyelination. This aberrant localisation of hyperphosphorylated neurofilament protein may contribute to neuronal dysfunction and degeneration in MS patients.

“This work is not new and reproduces what has been shown in other labs. It shows that the cortex or surface of the brain in MS is affected by pathological processes and affects the cytoskeleton of axons and nerves. Yet more evidence that MS is turning out to be more a disease of grey, rather  than white, matter. The problem we have is that the gray matter pathology is not picked up with routine imaging techniques.”

4 thoughts on “Research: more evidence for neurofilaments as a marker for progression”

  1. Prof G,Be warned – this is an attack on the world of MS research.COI – none. I am sick of CCSVI."Yet more evidence that MS is turning out to be more a disease of grey, rather than white, matter."I find this depressign and a sad indictment on the MS esearch community. 50 years of research, and no one can give me one fact about MS (apart from the fact that it is a bad disease):autoimmune / not autoimmune – dunno!primarily inflammator or neuro -degenerative – dunno!caused by a virus or gut bacteria -dunno?why more common in women – dunnowhite matter or grey matter disease – dunno!The annual MS conferences around the world pull in the crowds, but there is never any definitive research. There's something rotten in the world of MS research!We've had huge numbers of pathology studies e.g. Lesion Project. We've had the Tissue Bank. We've had huge advances in MRI etc etc. There are so called world calss MS research teams in Bristol, Cambridge, London, Edinburgh. Why can no one work out what's going on, work out how to stop, and work out how to repair it? Time to hand the disease voer to cancer research – the can't do any worse!

  2. autoimmune/not autoimmune Autoimmune yes Non-Autoimmune Yesprimarily inflammatory or neuro -degenerativeInflammatory and Neurodegenerativecaused by a virus or gut bacteria -Dunno-more likely to be virus than gut bacteria but keep options openwhy more common in women Hormoneswhite matter or grey matter disease Both

  3. Time to hand the disease over to cancer research – the can't do any worse!There is significantly more resource in cancer studies. There has been success in some forms of cancer overs have poor prognosis..

  4. There is a real cross over from drugs used in cancer to MS anyway- alemtuzumab, cladribine, mitoxantrone, cyclophosphamide.

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