Circulating miRNAs modulating systemic low-grade inflammation and affecting neurodegeneration

Abstract

Objective and design: Inflammatory processes are an important part of the etiology of many chronic diseases across various medical domains, including neurodegeneration. Understanding their regulation on the molecular level represents a major challenge. Regulatory microRNAs (miRNAs), have been recognized for their role in post-transcriptionally modulating immune-related pathways serving as biomarkers for numerous diseases. Subjects and Methods: This study aims to investigate the association between 176 plasma-circulating miRNAs and the blood-based immune markers C-reactive protein and fibrinogen within the general population-based SHIP-TREND-0 cohort (N = 801) and assess their impact on neurodegeneration in linear regression and moderation analyses. Results: We provide strong evidence for miRNA-mediated regulation, particularly in relation to fibrinogen, identifying 48 significant miRNAs with a pronounced over-representation in chronic inflammatory and neurological diseases. Additional moderation analyses explored the influence of the APOE ε4 genotype and brain white matter neurodegeneration on the association between miRNAs and inflammation. Again, significant associations were observed for fibrinogen with special emphasize on hsa-miR-148a-3p, known to impact on neuroinflammation. Conclusions: Our study suggests the involvement of several plasma-circulating miRNAs in regulating immunological markers while also being linked to neurodegeneration. The strong interplay between miRNAs and inflammation holds promising potential for clinical application in many immune-related neurodegenerative diseases.