Neurochemical biomarkers in amyotrophic lateral sclerosis

The diagnosis of amyotrophic lateral sclerosis (ALS) still relies mainly on clinical criteria. In present review we will provide an overview of neurochemical ALS biomarkers, which are in the most advanced position on the way towards inclusion into the clinical work-up.

The field of ALS neurology still lacks a neurochemical marker for routine clinical use. However, this is urgently needed, because it would help in diagnosis, prognostic stratification, and monitoring of drug response. Despite this lack of a routinely used biomarker, in the last decade significant progress has been made in the field. In particular, two molecules have been extensively studied - the light chain and the phosphorylated form of the heavy chain of neurofilaments, NFL and pNFH, respectively - which have demonstrated a high diagnostic performance and promising prognostic value and are therefore ready to be introduced into the clinical scenario. On the other hand, we still lack a neurochemical cerebrospinal fluid or blood biomarker reflecting TDP-43 pathology.

Neurofilaments seem to be ready for clinical use in the early and differential diagnosis of ALS. We also highlight still unresolved issues which deserve further investigation.