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Mult Scler. 2013 Feb;19(2):153-61. doi: 10.1177/1352458512451661. Epub 2012 Jun 21.

Accumulation of cortical hyperphosphorylated neurofilaments as a marker of neurodegeneration in multiple sclerosis.

Author information

1
MS Labs, Burden Centre, University of Bristol Institute of Clinical Neurosciences, Frenchay Hospital, UK. elizabeth.gray@bristol.ac.uk

Abstract

BACKGROUND:

Axonal loss and grey matter neuronal injury are pathological processes that contribute to disease progression in multiple sclerosis (MS). Axon damage has been associated with changes in the phosphorylation state of neurofilaments and the presence of axonal spheroids. 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.

PMID:
22723571
DOI:
10.1177/1352458512451661
[Indexed for MEDLINE]
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