Plasma microRNA biomarkers for detection of mild cognitive impairment: Biomarker Validation Study

Sheinerman, Kira S.; Tsivinsky, Vladimir G.; Abdullah, Laila; Crawford, Fiona; Umansky, Samuil R.

doi:10.18632/aging.100624

Cited by 110 publications

(105 citation statements)

References 28 publications

(36 reference statements)

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“…The means of precise coordination between these miRNAs in the regulation of hippocampaldependent learning merits additional study. Indeed, given their dysregulation within several neurocognitive disorders, miR-132/-212 may eventually serve as reliable biomarkers for cognitive dysfunction, or ultimately even as potential therapeutic targets for such disorders (Klein et al 2007;Cogswell et al 2008;Kim et al 2010;Wang et al 2011;Sheinerman et al 2013;Burgos et al 2014). …”

Section: Discussionmentioning

confidence: 99%

Targeted deletion of miR-132/-212 impairs memory and alters the hippocampal transcriptome

et al. 2016

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miR-132 and miR-212 are structurally related microRNAs that have been found to exert powerful modulatory effects within the central nervous system (CNS). Notably, these microRNAs are tandomly processed from the same noncoding transcript, and share a common seed sequence: thus it has been difficult to assess the distinct contribution of each microRNA to gene expression within the CNS. Here, we employed a combination of conditional knockout and transgenic mouse models to examine the contribution of the miR-132/-212 gene locus to learning and memory, and then to assess the distinct effects that each microRNA has on hippocampal gene expression. Using a conditional deletion approach, we show that miR-132/-212 double-knockout mice exhibit significant cognitive deficits in spatial memory, recognition memory, and in tests of novel object recognition. Next, we utilized transgenic miR-132 and miR-212 overexpression mouse lines and the miR-132/-212 double-knockout line to explore the distinct effects of these two miRNAs on the transcriptional profile of the hippocampus. Illumina sequencing revealed that miR-132/-212 deletion increased the expression of 1138 genes; Venn analysis showed that 96 of these genes were also downregulated in mice overexpressing miR-132. Of the 58 genes that were decreased in animals overexpressing miR-212, only four of them were also increased in the knockout line. Functional gene ontology analysis of downregulated genes revealed significant enrichment of genes related to synaptic transmission, neuronal proliferation, and morphogenesis, processes known for their roles in learning, and memory formation. These data, coupled with previous studies, firmly establish a role for the miR-132/-212 gene locus as a key regulator of cognitive capacity. Further, although miR-132 and miR-212 share a seed sequence, these data indicate that these miRNAs do not exhibit strongly overlapping mRNA targeting profiles, thus indicating that these two genes may function in a complex, nonredundant manner to shape the transcriptional profile of the CNS. The dysregulation of miR-132/-212 expression could contribute to signaling mechanisms that are involved in an array of cognitive disorders.

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Section: Discussionmentioning

confidence: 99%

Targeted deletion of miR-132/-212 impairs memory and alters the hippocampal transcriptome

et al. 2016

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“…Subsequently, we excluded studies with unhealthy controls (n=2) and the ones containing insufficient data (n=9) after carefully reading the full-texts and obtained eight articles for this meta-analysis [22][23][24][25][26][27][28][29].…”

Section: Literature Search Processmentioning

confidence: 99%

Circulating MicroRNA as Potential Source for Neurodegenerative Diseases Biomarkers

Yin²,

Xiao

et al. 2014

Mol Neurobiol

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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.

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“…Further, miR-134 plasma levels were significantly different between BD patients (medicated as well as drugfree) and controls [51]. miR-134 differential expression in SZ and BD further extends the list of brain diseases in which miR-134 seems to be deregulated: human anencephaly [52], glioblastoma [53,54], cognitive impairment [55], and epilepsy [56]. These wide-ranging implications of miR-134 in brain pathologies likely stem from its documented roles in cortical neuronal development [57], nerve growth cone guidance [58], dendritogenesis [59,60], learning, memory and plasticity [61,62].…”

Section: Deregulation Of Mirna Expression In Peripheral Blood Mononucmentioning

confidence: 73%

Deregulated microRNA expression in biospecimens from patients diagnosed with schizophrenia and bipolar disorder as a disease biomarker

Delalle

Kao

Choi

2014

Translational Neuroscience

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The biological markers for schizophrenia (SZ) and bipolar disorder (BD) would represent a precious tool in evaluating the risk for the development of these common neuropsychiatric diseases and, possibly, in the prevention of either disease episodes and/or treatment efficiency monitoring. Since both SZ and BD are diseases with a significant genetic component, the research over the last decades has focused on the genes with altered function in the central nervous system (CNS) of individuals suffering from these illnesses. Recently, however, small non-coding RNA molecules (microRNAs, miRNAs, miRs) were shown to regulate the expression of human CNS genes involved in cell processes and functions negatively affected in neuropsychiatric disorders, including synaptic development and maturation, learning and memory. Differentially expressed sets of miRNAs have been reported in the tissues of SZ and BD patients in comparison to controls suggesting the emergence of a novel class of potential biomarkers. Here we review the reports on the changes in miRNA expression in postmortem brain tissue and peripheral blood in SZ and BD. We also evaluate the potential of miRNA packaged in exosomes, signaling vesicles released by neurons and glia, to contribute to the disaggregation of the molecular machinery underlying mental disorders and provide clinically useful biomarkers.

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Plasma microRNA biomarkers for detection of mild cognitive impairment: Biomarker Validation Study

Cited by 110 publications

References 28 publications

Targeted deletion of miR-132/-212 impairs memory and alters the hippocampal transcriptome

Targeted deletion of miR-132/-212 impairs memory and alters the hippocampal transcriptome

Circulating MicroRNA as Potential Source for Neurodegenerative Diseases Biomarkers

Deregulated microRNA expression in biospecimens from patients diagnosed with schizophrenia and bipolar disorder as a disease biomarker

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