Neurofilaments: A Biomarker for Axonal Degeneration

The aim of this chapter is to explain why Neurofilaments (Nf) are a useful biomarker for axonal degeneration and can be used as a surrogate endpoint in clinical and experimental research. 2 Definitions Neurofilaments: Nf are proteins which are exclusively expressed in neurons and their adjacent axons. Nf are particularly abundant in the axon, where they are key building blocks of the axonal cytoskeleton. The complex protein chemistry of Nf is briefly described. Biomarker: A biomarker is a characteristic that is objectively measured and evaluated as an indicator of normal biologic processes, pathogenic processes, or pharmacological responses to therapeutic intervention. Surrogate endpoint : defines a biomarker that is intended to serve as a substitute of a clinically meaningful endpoint and is expected to predict the effect of a therapeutic intervention or the evolution of disease. 2 Quantitative description Nf are obligate heteropolymers that are composed of 4 subunits: a light (NfL), a medium (NfM), a heavy (NfH) [1] chain and also alpha-internexin [2, 3]. In some cases, peripherin may be added to the list [2]. These subunits differ not only in their molecular weight, but also in their functional properties, as discussed below