Age Correlation of Serum/Plasma microRNAs is Lost in Amyotrophic Lateral Sclerosis
Background:Amyotrophic lateral sclerosis (ALS) is a devastating neuromuscular disease with an enigmatic pathogenesis. The discovery of universal microRNA biomarkers has been challenged by inconsistent and heterogeneous results across studies, possibly due to confounding factors and interpopulation differences. While most biomarker studies involved patients of European ancestry, the current study is the first pilot microRNomics study to explore circulating microRNAs in Egyptian sporadic ALS patients in comparison to Europeans.Methods:Small RNA sequencing of plasma microRNAs was conducted for 24 Egyptian sporadic ALS patients and their matched controls. Microarray data from 18 German patients and their controls were reanalyzed, and results were validated in independent cohorts using RT-qPCR.Results:Dysregulated miRNAs showed no overlap between healthy aging and ALS in the Egyptian cohorts. Interestingly, out of 151 microRNAs, 41 significantly correlated with age in healthy Egyptians versus only 6 in Egyptian ALS patients (p<0.0001). This loss of age correlation in ALS was also evident in the German population, and could also be validated by targeted approaches.Conclusion:This new finding of loss of age correlation of circulating microRNAs in ALS, as proven in two different populations, questions the possibility of developing serum/plasma miRNA biomarkers in ALS for clinical use.