MicroRNA Expression Signature in Mild Cognitive Impairment Due to Alzheimer’s Disease

Abstract

AbstractMild cognitive impairment (MCI) defines an intermediate state between normal ageing and dementia, including Alzheimer’s disease (AD). Identification of MCI subjects who will progress to AD (MCI-AD) is today of crucial importance, especially in light of the possible development of new pathogenic therapies. Several evidences suggest that miRNAs could play relevant roles in the biogenesis of AD, and the links between selected miRNAs and specific pathogenic aspects have been partly explored. In this study, we analysed the composition of microRNA transcriptome in blood, serum and cerebrospinal fluid samples from MCI-AD subjects, from an enriched small RNA library. Real-time qPCR from MCI-AD and AD patients and normal controls was performed to profile miRNA expression. In particular, four microRNAs, hsa-mir-5588-5p, hsa-mir-3658, hsa-mir-567 and hsa-mir-3908, among all selected microRNAs, are dysregulated. Hsa-mir-567 was found to be differentially expressed in cerebrospinal fluid samples, blood and serum from MCI-AD patients, showing the highest fold change and statistical significance. Target prediction analysis have been performed to evaluate mRNAs whose expression was controlled by miRNAs found to be dysregulated here, showing that hsa-mir-567 target genes are functionally active in neuronal cells. We propose that miRNA profiles found in samples from MCI-AD patients might be relevant for a better understanding of AD-related cognitive decline and could lead to set up suitable and potential biomarkers for MCI-AD progression to AD.