Axonal maturaion in development—I. Characterization of monoclonal antibodies reacting with axon-specific neurofilament epitopes

Monoclonal antibodies reacting with the high molecular weight neurofilament polypeptides (NF 150K and NF 200K) were obtained upon immunization with NF 150K and NF 200K isolated from bovine spinal cord by anion exchange chromatography. The five monoclonal antibodies obtained with NF 200K stained only axons. With three monoclonals the reactivity was abolished by digestion with phosphatase and by dilution of the supernatants in sodium potassium phosphate. The nine monoclonal antibodies obtained upon immunization with NF 150K stained both high molecular weight neurofilament polypeptides on immunoblots of bovine and rat spinal cord extracts with the exception of one monoclonal only reacting with the homologous antigen. The antibodies could be divided into two groups, axon-specific and conventional. Conventional antibodies decorated neurofilaments regardless of their location, i.e. axons, perikarya and dendrites. With all these antibodies the immunostaining was not affected by phosphatase digestion of neurofilament protein nor by dilution of the supernatants in sodium potassium phosphate. Axon-specific antibodies reacting with both NF 150K and NF 200K in rat spinal cord only stained the heterologous antigen (NF 200K) in rat optic nerve and sciatic nerve extracts. We suggest that some axon-specific neurofilament antibodies recognize neurofilament modifications other than phosphorylation; or, alternatively that they react with phosphorylated epitopes not accessible to phosphate or to exogenous phosphatases. Furthermore, we suggest that some neurofilament modifications do not occur uniformly throughout the nervous system.     

Emerging imaging and liquid biomarkers in multiple sclerosis

The advent of highly effective disease modifying therapy has transformed the landscape of multiple sclerosis (MS) care over the last two decades. However, there remains a critical, unmet need for sensitive and specific biomarkers to aid in diagnosis, prognosis, treatment monitoring, and the development of new interventions, particularly for people with progressive disease. This review evaluates the current data for several emerging imaging and liquid biomarkers in people with MS. MRI findings such as the central vein sign and paramagnetic rim lesions may improve MS diagnostic accuracy and evaluation of therapy efficacy in progressive disease. Serum and cerebrospinal fluid levels of several neuroglial proteins, such as neurofilament light chain and glial fibrillary acidic protein, show potential to be sensitive biomarkers of pathologic processes such as neuro-axonal injury or glial-inflammation. Additional promising biomarkers, including optical coherence tomography, cytokines and chemokines, microRNAs, and extracellular vesicles/exosomes, are also reviewed, among others. Beyond their potential integration into MS clinical care and interventional trials, several of these biomarkers may be informative of MS pathogenesis and help elucidate novel targets for treatment strategies.