Protein biomarkers for the diagnosis and prognosis of Amyotrophic Lateral Sclerosis.

Amyotrophic Lateral Sclerosis (ALS) is the most common motor neuron disease, still incurable. The disease is highly heterogenous both genetically and phenotypically. Therefore, developing efficacious treatments is challenging in many aspects because it is difficult to predict the rate of disease progression and stratify the patients to minimize statistical variability in clinical studies. Moreover, there is a lack of sensitive measures of therapeutic effect to assess whether a pharmacological intervention ameliorates the disease. There is also urgency of markers that reflect a molecular mechanism dysregulated by ALS pathology and can be rescued when a treatment relieves the condition. Here, we summarize and discuss biomarkers tested in multicentered studies and across different laboratories like neurofilaments, the most used marker in ALS clinical studies, neuroinflammatory-related proteins, p75ECD, p-Tau/t-Tau, and UCHL1. We also explore the applicability of muscle proteins and extracellular vesicles as potential biomarkers. • Amyotrophic Lateral Sclerosis (ALS) is the most common motor neuron disease. • There is an urgent need to identify biomarkers for ALS. • Neurofilaments show very good performances for diagnosis and prognosis. • Other markers are under analysis across multiple laboratories for validation. [ABSTRACT FROM AUTHOR]