Profiling non-coding RNA expression in cerebrospinal fluid of amyotrophic lateral sclerosis patients

Finding objective biomarkers for the fatal neurodegenerative disease amyotrophic lateral sclerosis or motor neuron disease (ALS/MND) is critical for aiding diagnosis, drug development and clinical trials in addition to providing insight into pathology. Non-coding RNA (ncRNA) transcripts including microRNA, piwi-interacting RNA and transfer RNA are present in human biofluids and are key candidates as biomarkers, supported by our previous work identifying dysregulated ncRNA in serum of ALS patients. As serum may not reflect central nervous system pathology, we sought to identify ncRNA biomarker candidates in cerebrospinal fluid (CSF) which may provide new insight into the disease pathology. Small RNA-seq was undertaken on CSF samples from our Oxford Study for Biomarkers of ALS cohort. We found a range of ncRNA that were dysregulated in the RNA-seq screen, but these failed to be validated, and in some cases detected, using RT-qPCR. Additionally, the ncRNA biomarker candidates we have previously identified as being dysregulated in the serum of ALS patients showed no change in CSF or correlation to serum. Together, this study suggests the CSF may not be the source of dysregulated ncRNA in the serum and highlights the difficulty in identifying ncRNA in CSF as biomarkers for ALS.