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.”