Neurodegenerative markers : insights into multiple sclerosis
Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system (CNS) characterised pathologically by inflammation, demyelination and variable degrees of axonal loss and gliosis. Remyelination, axonal and synaptic plasticity have been identified as mechanisms underlying functional recovery. MS typically follows a chronic course, in the sense that new episodes or steady progression are the rule. Currently radiological surrogates of inflammation, demyelination and axonal loss are available, but these correlate only modestly with the development of cumulative disability. In this thesis, potential brain specific protein (BSP) markers for these pathological processes are identified and compared to existing magnetic resonance (MR) markers. OBJECTIVES: Levels of the nervous system proteins S100B (astrocytic activation), glial fibrillary acidic protein (GFAP astrogliosis), neurofilaments (axonal marker) and ferritin (microglial activation) and other inflammatory markers (i.e. anti-myelin antibodies) were measured. These values were correlated with both histopathological measurements in post-mortem specimens and MR imaging measures in patients with MS. Histology and immunochemistry of tissue sections characterised normal and pathological CNS and localized the extent of demyelinating plaques.