Circulating miR-181 is a prognostic biomarker for amyotrophic lateral sclerosis

Iddo Magen, Nancy Sarah Yacovzada, Eran Yanowski, Anna Coenen-Stass, Julian Grosskreutz, Ching Hua Lu, Linda Greensmith, Andrea Malaspina, Pietro Fratta, Eran Hornstein*

*Corresponding author for this work
10 Citations (Scopus)


Amyotrophic lateral sclerosis (ALS) is a relentless neurodegenerative disease of the human motor neuron system, where variability in progression rate limits clinical trial efficacy. Therefore, better prognostication will facilitate therapeutic progress. In this study, we investigated the potential of plasma cell-free microRNAs (miRNAs) as ALS prognostication biomarkers in 252 patients with detailed clinical phenotyping. First, we identified, in a longitudinal cohort, miRNAs whose plasma levels remain stable over the course of disease. Next, we showed that high levels of miR-181, a miRNA enriched in neurons, predicts a greater than two-fold risk of death in independent discovery and replication cohorts (126 and 122 patients, respectively). miR-181 performance is similar to neurofilament light chain (NfL), and when combined together, miR-181 + NfL establish a novel RNA–protein biomarker pair with superior prognostication capacity. Therefore, plasma miR-181 alone and a novel miRNA–protein biomarker approach, based on miR-181 + NfL, boost precision of patient stratification. miR-181-based ALS biomarkers encourage additional validation and might enhance the power of clinical trials.

Original languageEnglish
JournalNature Neuroscience
Issue number11
Pages (from-to)1534-1541
Number of pages8
Publication statusPublished - 11.2021

Research Areas and Centers

  • Academic Focus: Center for Brain, Behavior and Metabolism (CBBM)
  • Centers: Center for Neuromuscular Diseases


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