MicroRNA Expression Signature in Mild Cognitive Impairment Due to Alzheimer\u2019s Disease

Bruna De Felice,Valeria Di Onofrio,Concetta Montanino,Simona Bonavita,Cinzia Coppola,Mariano Oliva

doi:10.1007/s12035-020-02029-7

Abstract

Mild 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.

Highlights

Neurodegenerative diseases, such as Alzheimer’s disease (AD), are age-related disorders whose prevalence is growing worldwide due to the progressive ageing of the population, constituting a very important public health problem
According to the primary aim of characterizing the small non-coding RNA molecules (sncRNA) signature from peripheral blood of Mild cognitive impairment (MCI)-AD cases, we evaluated a set of 18 MCI subjects who will progress to AD (MCI-AD) patients by sncRNA cloning
Using real-time strategy, we detected that, among these, only hsa-miR-567 has been found to be highly expressed in blood, leukocytes and CSF, substantially upregulated with a twofold induction in the group of MCI-AD patients compared with the other selected miRNAs (p* < 0.05) (Fig. 2)

Summary

Introduction

Neurodegenerative diseases, such as Alzheimer’s disease (AD), are age-related disorders whose prevalence is growing worldwide due to the progressive ageing of the population, constituting a very important public health problem. Mild cognitive impairment (MCI) is a condition characterized by a subjective experience of progressive decline of cognitive functions, accompanied by objective evidence of altered cognitive performance, without significant impairment of daily life activities [1]. Some miRNAs are highly expressed in specific neuronal compartments, including axons, dendrites and synapses [6, 7], where they are essential for normal neuronal function and survival [8]. Impaired expression of several miRNAs has been found in various neurodegenerative conditions, including AD, Parkinson’s disease and amyotrophic lateral sclerosis [9,10,11,12], as well as in nonneurodegenerative dementias such as vascular dementia [13]; only very few studies have focused on the earliest stages of the disease. MiRNAs have been shown to be stable in blood samples [14], and measurements of altered miRNA expression patterns in blood, serum and CSF have become promising novel diagnostic tools and prognostic biomarkers for various neurological diseases [15]

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Conclusion