Circulating MicroRNA as Potential Source for Neurodegenerative Diseases Biomarkers

Abstract

An increasing number of circulating micro-ribonucleic acids (microRNAs, miRNAs) have been discovered its potential as biomarkers to diagnose neurodegenerative diseases (NDs) by many researchers. However, there were obvious inconsistencies among previous studies, and thus we performed this meta-analysis to evaluate whether miRNA is an effective biomarker with high accuracy to diagnose the NDs. PubMed, MEDLINE, EMBASE, the Cochrane Library, and other related databases were used to search eligible articles. The data of sensitivity and specificity were employed to plot the summary receiver operator characteristic (SROC) curve and calculate the area under the SROC curve (AUC). I (2) test were used to estimate the heterogeneity among different studies. In addition, the possible sources of heterogeneity were further explored by subgroup analyses and meta-regression. All analyses were performed by STATA 12.0 software. In this meta-analysis, eight publications with 459 NDs patients and 340 healthy controls were included to investigate the diagnostic performance of circulating miRNAs for NDs. The overall sensitivity and specificity, positive likelihood ratio (PLR), negative likelihood ration (NLR), and diagnostic odds ratio (DOR) were 0.83 (95% confidence interval (CI) 0.77-0.88), 0.87 (95% CI 0.83-0.89), 6.2 (95% CI 4.9-7.9), 0.19 (95% CI 0.14-0.27), 33 (95% CI 20-52), and 0.91 (95% CI: 0.88-0.93), respectively. The overall SROC curve was plotted with AUC of 0.91 (95% CI 0.88-0.93), which indicated an excellent diagnostic performance of circulating miRNA for NDs. Subgroup analysis based on miRNA profile demonstrated that multiple-miRNA assay had higher diagnostic accuracy for NDs when compared with single-miRNA assay. In conclusion, the circulating miRNAs may be the potential biomarkers in the clinical diagnosis of NDs, and the diagnostic accuracy would be better by using multiple-miRNA assay. However, large-scale studies are still needed to explore the relation between the circulating miRNA dysregulation and the pathological mechanism of NDs.

MicroRNA-212-5p Prevents Dopaminergic Neuron Death by Inhibiting SIRT2 in MPTP-Induced Mouse Model of Parkinson’s Disease

“…There is lack of miR-212-5p study besides a recently study reported that miR-212-5p was related to fungal infections ( Dix et al, 2017 ). Recently, besides the potential of miRNAs as biomarkers, miRNAs are also gaining attention for their therapeutic potential with far-reaching roles in neurodegenerative diseases ( Zi et al, 2015 ). Here, we found stereotactic injection of miR-212-5p mimics into the midbrain of mice could prevent dopaminergic neuron damage and loss.…”

Genome-wide identification of microRNA-related variants associated with risk of Alzheimer’s disease

“…Recent studies have shown the critical role of miRNAs in neuronal development and function 19 26 27 28 . In addition, a number of miRNAs have been reported to be implicated in the development of AD 7 8 9 10 11 12 . However, these studies were mainly focused on differentially expressed miRNAs and target genes using expression arrays in a small number of samples.…”

“…They have been shown to be involved in biological and pathological processes in the brain789. In addition, a number of dysregulated miRNAs have been reported to be associated with AD and are suggested as potential diagnostic biomarkers for AD101112. MiRNAs repress translation or decrease the stability of target messenger RNAs (mRNAs), by binding of the nucleotides 2–8 from their 5′ end (known as the seed region) to complementary sequences in the 3′ UTR regions of target mRNAs13.…”

MicroRNAs in Disease

“…Moreover, miR-384 which targets APP and BACE-1 was isolated from the cerebrospinal fl uid of patients with mild cognitive impairment and Alzheimer's type dementia and was found to be signifi cantly lower compared to controls [ 134 ]. In a recent meta-analysis of eight studies in search of the diagnostic validity of biomarkers in neurodegeneration, authors found contrasting results between different studies and suggest the usage of assays taking into account multiple miRNAs instead of a single species assay [ 135 ]. In other disorders such as multiple sclerosis, miR-21, miR-142-3p, miR-146a/b, miR-155 and miR-326 were found to be elevated in mononuclear blood cells and white matter brain regions in MS patients (reviewed in [ 136 ]).…”