Plasma microRNAs as potential biomarkers in early Alzheimer disease expression

Abstract

Abstract The microRNAs (miRNAs) are potential biomarkers for complex pathologies due to their involvement in the regulation of several pathways. Alzheimer Disease (AD) requires new biomarkers in minimally invasive samples that allow an early diagnosis. The aim of this work is to study miRNAS as potential AD biomarkers and their role in the pathology development. In this study, participants (n = 46) were classified into mild cognitive impairment due to AD (MCI-AD, n = 19), preclinical AD (n = 8) and healthy elderly controls (n = 19), according to CSF biomarkers levels (amyloid β42, total tau, phosphorylated tau) and neuropsychological assessment. Then, plasma miRNAomic expression profiles were analysed by Next Generation Sequencing. Finally, the selected miRNAs were validated by quantitative PCR (q-PCR). A panel of 11 miRNAs was selected from omics expression analysis, and 8 of them were validated by q-PCR. Individually, they did not show statistically significant differences among participant groups. However, a multivariate model including these 8 miRNAs revealed a potential association with AD for three of them. Specifically, relatively lower expression levels of miR-92a-3p and miR-486-5p are observed in AD patients, and relatively higher levels of miR-29a-3p are observed in AD patients. These biomarkers could be involved in the regulation of pathways such as synaptic transmission, structural functions, cell signalling and metabolism or transcription regulation. Some plasma miRNAs (miRNA-92a-3p, miRNA-486-5p, miRNA-29a-3p) are slightly dysregulated in AD, being potential biomarkers of the pathology. However, more studies with a large sample size should be carried out to verify these results, as well as to further investigate the mechanisms of action of these miRNAs.