BACKGROUND Peripheral blood microRNAs (miRNA) have been identified as potential biomarkers for Alzheimer's disease (AD). Study results have generally been inconsistent and limited by sample heterogeneity. The aim of this study is to establish candidate blood miRNA biomarkers for AD by comparing differences in miRNA expression between participants with brain amyloid imaging-defined AD and normal cognition. METHODS Blood RNA was extracted from a subset of participants from the Australian Imaging Biomarkers Lifestyle Study of Ageing cohort (AIBL) with brain amyloid imaging results. MiRNA profiling was performed using small RNA sequencing on 71 participants, comprising 40 AD with high brain amyloid burden on imaging (amyloid positive) and 31 cognitively normal controls with low brain amyloid burden (amyloid negative). Cross-sectional comparisons were made between groups to examine differential miRNA expression levels using Fisher's exact tests. Replication of results was undertaken using a publicly available dataset of blood miRNA data of AD and controls. In silico analysis of downstream messenger RNA targets of candidate miRNAs was performed to elucidate potential biological function. RESULTS After quality control, 816 miRNAs were available for analysis. There were 71 significantly differentially expressed miRNAs between the AD and control groups (p < 0.05). Two of these miRNAs, miR-146b-5p and miR-15b-5p, were also significant in the replication cohort. Pathways analysis showed these miRNAs to be involved in innate immune system and regulation of the cell cycle, respectively, both of which have relevance to AD pathogenesis. CONCLUSION Blood miR-146b-5p and miR15b-5p showed consistent differential expression in AD compared to controls. Further replication and translational studies in strictly phenotyped cohorts are needed to establish their role as biomarkers for AD to have clinical utility.

中文翻译：

---

脑淀粉样蛋白成像定义的阿尔茨海默氏病和对照中血液miRNA的差异表达。

背景技术外周血微小RNA（miRNA）已经被鉴定为阿尔茨海默氏病（AD）的潜在生物标记。研究结果通常不一致，并受样品异质性的限制。这项研究的目的是通过比较大脑淀粉样蛋白成像定义的AD与正常认知参与者之间的miRNA表达差异来建立AD的候选血液miRNA生物标记。方法从澳大利亚成像生物标志物生活方式研究队列研究（AIBL）的一部分参与者中提取血液RNA，并进行脑淀粉样蛋白成像。使用71位参与者的小RNA测序对MiRNA进行分析，其中包括40位AD且影像学上的大脑淀粉样蛋白负担高（淀粉样蛋白阳性）和31位认知正常的大脑淀粉样蛋白负担低的对照（淀粉样蛋白阴性）。使用Fisher精确检验在两组之间进行横截面比较，以检查差异miRNA表达水平。使用可公开获得的AD和对照血液miRNA数据集进行结果复制。对候选miRNA的下游信使RNA靶进行计算机分析，以阐明潜在的生物学功能。结果质量控制后，有816个miRNA可用于分析。AD组和对照组之间存在71个差异显着表达的miRNA（p <0.05）。这些miRNA中的两个miR-146b-5p和miR-15b-5p在复制队列中也很重要。途径分析表明，这些miRNA分别参与先天免疫系统和细胞周期调控，两者均与AD发病机制有关。结论血液中的miR-146b-5p和miR15b-5p与对照组相比在AD中表现出一致的差异表达。需要进一步在严格表型队列中进行复制和翻译研究，以确立其作为AD的生物标志物的作用，以具有临床效用。