MicroRNAs as Biomarkers in Amyotrophic Lateral Sclerosis

Abstract

Amyotrophic lateral sclerosis (ALS) is an incurable and fatal disorder characterized by the progressive loss of motor neurons in the cerebral cortex, brain stem, and spinal cord. Sporadic ALS form accounts for the majority of patients, but in 1⁻13.5% of cases the disease is inherited. The diagnosis of ALS is mainly based on clinical assessment and electrophysiological examinations with a history of symptom progression and is then made with a significant delay from symptom onset. Thus, the identification of biomarkers specific for ALS could be of a fundamental importance in the clinical practice. An ideal biomarker should display high specificity and sensitivity for discriminating ALS from control subjects and from ALS-mimics and other neurological diseases, and should then monitor disease progression within individual patients. microRNAs (miRNAs) are considered promising biomarkers for neurodegenerative diseases, since they are remarkably stable in human body fluids and can reflect physiological and pathological processes relevant for ALS. Here, we review the state of the art of miRNA biomarker identification for ALS in cerebrospinal fluid (CSF), blood and muscle tissue; we discuss advantages and disadvantages of different approaches, and underline the limits but also the great potential of this research for future practical applications.

Keywords: amyotrophic lateral sclerosis (ALS); biomarker; cerebrospinal fluid (CSF); circulating miRNAs; microRNA; muscle biopsy.

Figure 1

MicroRNA (miRNA)-based biomarkers in amyotrophic lateral sclerosis (ALS) patients. Schematic workflow to identify possible miRNAs as biomarkers starting from ALS patients’ sample using different quantitative approaches. The comparison among the common characteristics of miRNA detection platforms is summarized in the figure. Sensibility, specificity and throughput are classified as follows: +++ (very high), ++ (moderate), +/++ (moderate to low) and + (low). Abbrevations: qRT-PCR, quantitative Real-Time Polymerase Chain Reaction; NGS, Next Generation Sequencing.