The Use and Potential of pNF-H as a General Blood Biomarker of Axonal Loss: An Immediate Application for CNS Injury

Excerpt

This chapter describes the unusual protein chemical properties of the phosphorylated axonal form of the heavy neurofilament subunit NF-H (pNF-H). I show how these properties conspire to make this protein an excellent biomarker of ongoing chronic and acute axonal loss useful in clinical and research contexts. pNF-H can be detected by ELISA not only in cerebrospinal fluid but also in plasma and serum. I summarize neurological damage and disease states in which this protein has been measured in elevated and informative levels in blood. Finally, I use this biomarker to discuss some of the problems, questions and opportunities associated with the biomarker field in general, and highlight some areas which require further research on this and other potential biomarkers.

There has been much interest in the development of assays that can reflect the seriousness and type of central nervous system (CNS) injury. Ideally, such assays could rapidly inform a researcher or a clinician about ongoing challenges to the CNS of an individual. Such challenges may result from chronic or acute events, and different kinds of assays would inform about different types of events. Much recent thought has focused on sports-related injuries, the issue being whether a sportsman should carry on playing following a mild head injury. As other examples, diseases such as multiple sclerosis (MS) tend to be variable in different patients and several different therapies are available. Understanding which therapy is effective would aid in patient treatment and could be assessed from an appropriate test. Potential rapid assays include advanced magnetic, X-ray and radiochemical-based imaging methods that will not be discussed here. Rather, I will focus on the detection of substances in biological fluids with the potential to provide information about CNS status, response to therapy, and prognosis. So how does this field of research stand? There are many excellent and comprehensive reviews in this area (Dash et al., 2011; Kovesdi et al., 2010; Kuhle et al., 2011; Mondello et al., 2011), but I will write on just one particular biomarker, the phosphorylated axonal form of the major neurofilament subunit NF-H (pNF-H). This biomarker has some particularly favorable properties that allow detection not only in cerebrospinal fluid (CSF), but also in blood. I will also attempt to raise important issues that have had little exposure to date and that may point the way to future advances with this particular biomarker and by analogy to other biomarkers.