Department of Psychiatry and Psychotherapy, University Medicine Greifswald, 17475 Greifswald, Germany; German Centre for Neurodegenerative Diseases (DZNE), Site Rostock/Greifswald, 17475 Greifswald, Germany.
Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, 17475 Greifswald, Germany; German Centre for Cardiovascular Research (DZHK), Partner Site Greifswald, 17475 Greifswald, Germany.
Prog Neuropsychopharmacol Biol Psychiatry. 2024 Dec 20;135:111130. doi: 10.1016/j.pnpbp.2024.111130. Epub 2024 Aug 28.
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.
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.
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.
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.
炎症过程是包括神经退行性变在内的多个医学领域许多慢性疾病发病机制的重要组成部分。了解其在分子水平上的调控是一项重大挑战。调节 microRNA（miRNA）已因其在后转录水平上调节免疫相关途径的作用而被认可，可作为许多疾病的生物标志物。
本研究旨在调查 176 种循环血浆 miRNA 与基于人群的 SHIP-TREND-0 队列（N=801）中普通人群血液免疫标志物 C 反应蛋白和纤维蛋白原之间的关联，并在线性回归和调节分析中评估它们对神经退行性变的影响。
我们提供了 miRNA 介导的调节的有力证据，特别是与纤维蛋白原相关的调节，确定了 48 种与慢性炎症和神经疾病显著相关的 miRNA，表现出明显的过度表达。额外的调节分析探讨了 APOE ε4 基因型和脑白质神经退行性变对 miRNA 与炎症之间关联的影响。同样，在纤维蛋白原与 hsa-miR-148a-3p 之间观察到显著的关联，hsa-miR-148a-3p 已知会影响神经炎症。
我们的研究表明，几种循环血浆 miRNA 参与调节免疫标志物，同时与神经退行性变有关。miRNA 与炎症之间的强烈相互作用为许多与免疫相关的神经退行性疾病的临床应用提供了有希望的潜力。
