Abstract: Hyperexcitation due to defective A-to-I editing of GRIA2 has been reported in motor neurons of amyotrophic lateral sclerosis (ALS) patients. To clarify the miRNA profile, specifically A-to-I editing, in extracellular vesicles (EVs) derived from the body fluids of patients with ALS. Neuronal EVs were isolated from the serum and cerebrospinal fluid (CSF) of 20 patients with sporadic ALS (SALS) (time-course samples) and 10 healthy controls who participated in the ROPALS trial, and miRNA-seq analysis was performed after extracting the miRNAs in the EVs. A-to-I editing was detected in miRNAs in neuronal-derived exosomes and the A-to-I editing rate was calculated. The A-to-I editing rate of miRNAs in the neuronal-derived exosomes of SALS patients was significantly lower than that of healthy controls, but was significantly increased in CSF by ropinirole treatment. The diagnostic performance of miRNAs in neuronal-derived exosomes by A-to-I editing rate was AUC 0.690 for Blood and AUC 0.791 for CSF. The random forest classifier achieved diagnostic performance of AUC 1.00 for Blood and AUC 0.99 for CSF. Measuring miRNAs derived from EVs in the body fluids of ALS patients may contribute to disease diagnosis and evaluation of disease progression. As a diagnostic biomarker, the A-to-I editing rate by GRIA2 mRNA in CSF has been proposed. miRNAs can be diagnosed not only in CSF but also in blood samples and are detectable in all cases. miRNAs of the exosome in CSF may be useful as pharmacodynamic useful as markers in ropinirole.
Funding Source: This study was supported by the grant support from Japan Society for the Promotion of Science (JSPS) and Japan Agency for Medical Research and Development (AMED).
