Poster Presentation Australasian Extracellular Vesicles Conference 2018

Exosomal miRNA biomarkers for Amyotrophic Lateral Sclerosis (#91)

Natasha Vassileff 1 , Mitch Shambrook 1 , Laura J Vella 2 , Amirmohammad N Nasiri Kenari 1 , Jacky Chan 2 , Catriona McLean 2 , Lesley Cheng 1 , Andrew F Hill 1
  1. Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Bundoora, VIC, Australia
  2. Howard Florey Institute of Neuroscience and Mental Health, Parkville, Victoria, Australia

The repertoire of exosomal miRNAs that may be deregulated in Motor Neuron Disease (MND) patients could represent potential biomarkers for this neurodegenerative disease. MicroRNAs (miRNAs) are small non-coding RNAs that post-transcriptionally regulate gene expression, and their deregulation has been associated with the pathogenesis of neurodegenerative diseases. Additionally, miRNAs have been documented to be secreted in exosomes, a form of extracellular vesicles involved in inter-cellular communication. Therefore, by observing the miRNA expression of brain derived exosomes (BDEs) isolated from ALS subjects, deregulated miRNAs can be identified and their potential contribution to the spread of the disease can be determined. These BDEs were isolated from human post-mortem ALS (n=9) and neuroloical control (HC) (n=6) brain tissue in order to determine which miRNAs were differentially expressed in the ALS BDEs. Following thorough characterisation, the BDEs successfully met the minimum criteria required by The International Society for Extracellular Vesicles to be classified as exosomes. The BDEs’ small RNA content was subsequently sequenced by next-generation sequencing (NGS), allowing for a panel of ALS associated miRNAs to be identified in the ALS BDEs. To determine whether the panel of ALS associated BDE miRNAs are also detected in the periphery, neural derived exosomes (NDEs) isolated from serum will also be sequenced. Here, we have also optimised the isolation of NDEs. If the same miRNAs differentially expressed in the ALS BDEs are observed in the ALS NDEs then this may enable a set of potential ALS blood-based biomarkers to be determined.