MicroRNA alterations in chronic traumatic encephalopathy and amyotrophic lateral sclerosis

Abstract

Repetitive head impacts (RHI) and traumatic brain injuries are risk factors for the neurodegenerative diseases chronic traumatic encephalopathy (CTE) and amyotrophic lateral sclerosis (ALS). Although distinct, these diseases can share an overlapping pathology (e.g. TDP-43) and affect similar brain regions. However, the pathways involved and biomarkers for diagnosis are unknown. MicroRNAs (miRNAs) are altered in disease, are involved in gene regulation, and may be useful as stable biomarkers. Thus, we set out to determine associations between miRNA levels and disease state within the prefrontal cortex in a group of deceased participants with no pathology (controls), CTE, ALS, or comorbid CTE+ALS. Of the 47 miRNAs previously implicated in neurological disease, 27 were significantly different between pathology groups. Of these, seventeen (63%) were upregulated in both ALS and CTE and included miRNAs involved in inflammatory, apoptotic and cell growth/differentiation pathways. Nine miRNAs (33%) were specifically upregulated only in ALS as opposed to only one miRNA (4%) with CTE specific upregulation. Surprisingly, few miRNAs (14%) were significantly altered in comorbid CTE+ALS, which may reflect the milder disease present at death in participants with both conditions. Overall, we found patterns of miRNA expression that are common and unique to CTE and ALS and that suggest common pathways of pathogenesis.