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


OBJECTIVE
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.
MS Labs, Burden Centre, University of Bristol Institute of Clinical Neurosciences, Frenchay Hospital, UK. elizabeth.gray@bristol.ac.uk
Elizabeth
E
Gray
Claire
C
Rice
Helen
H
Nightingale
Mark
M
Ginty
Kelly
K
Hares
Kevin
K
Kemp
Nicki
N
Cohen
Seth
S
Love
Neil
N
Scolding
Alastair
A
Wilkins
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001369:Axons / Q000473:pathology; D015153:Blotting, Western; D002540:Cerebral Cortex / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000378:metabolism* / Q000473:pathology; D019636:Neurodegenerative Diseases / Q000473:pathology*; D016900:Neurofilament Proteins / Q000276:immunology / Q000378:metabolism*; D009474:Neurons / Q000473:pathology; D016612:Paraffin Embedding; D010766:Phosphorylation; D014015:Tissue Banks
D016900:Neurofilament Proteins; C051774:neurofilament protein H