Dataset Information

A Panel of Exosome-Derived miRNAs of Cerebrospinal Fluid for the Diagnosis of Moyamoya Disease.

ABSTRACT: Background:Moyamoya disease (MMD) is an important cause of stroke in children and young adults in Asia. To date, diagnosis remains challenging due to varying clinical manifestations and unknown pathogenesis. The study aims to identify cerebrospinal fluid (CSF) exosomal microRNAs (exomiRs) that can serve as a novel diagnostic biomarker for diagnosis and assess its clinical applications. Methods:CSF samples were taken from 31 MMD patients and 31 healthy controls. Initial screening of miRNA expression was performed on samples pooled from MMD patients and controls using microarray and validated using quantitative reverse transcription polymerase chain reaction (qRT-PCR). The diagnostic accuracy of the potential exosomal miRNAs was evaluated using receiver operating characteristic curve analyses in an independent patient cohort. The potential pathways regulated by the miRNAs was also determined using bioinformatics analysis. Results:The microarray results demonstrated that six exomiRs were dysregulated in the MMD patients compared to the controls. Using qRT-PCR, we validated four of the miRNAs (miR-3679-5p, miR-6165, miR-6760-5p, and miR-574-5p) as a biomarker for MMD diagnosis. The four exomiRs showed enhanced sensitivity (75%) and specificity (93.75%) in terms of differentiating MMD patients from healthy subjects [area under the curve (AUC) = 0.9453]. Pathway enrichment analysis for potential targets of six exomiRs identified proteins involved in cell adhesion and junction formation in the brain. Conclusions:We identified a novel and highly sensitive exomiRs signature for MMD detection and explored its potential targets using bioinformatics analysis.

SUBMITTER: Wang G

PROVIDER: S-EPMC7546773 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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A Panel of Exosome-Derived miRNAs of Cerebrospinal Fluid for the Diagnosis of Moyamoya Disease.

Wang Gang G Wen Yunyu Y Faleti Oluwasijibomi Damola OD Zhao Qingshun Q Liu Jingping J Zhang Guozhong G Li Mingzhou M Qi Songtao S Feng Wenfeng W Lyu Xiaoming X

Frontiers in neuroscience 20200925

<h4>Background</h4>Moyamoya disease (MMD) is an important cause of stroke in children and young adults in Asia. To date, diagnosis remains challenging due to varying clinical manifestations and unknown pathogenesis. The study aims to identify cerebrospinal fluid (CSF) exosomal microRNAs (exomiRs) that can serve as a novel diagnostic biomarker for diagnosis and assess its clinical applications.<h4>Methods</h4>CSF samples were taken from 31 MMD patients and 31 healthy controls. Initial screening o ...[more]

PMID: 33100957

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Project description:We aimed to investigate whether mitochondrial dysfunction in extracellular cerebrospinal fluid (CSF), which is associated with autophagy and mitophagy, might be involved in neurological outcomes in adult patients with hemorrhagic moyamoya disease (MMD) whose pathogenesis related to poor outcomes is not well-known. CSF samples were collected from 43 adult MMD patients and analyzed according to outcomes at 3 months. Fluorescence-activated cell sorter analysis (FACS) and the JC-1 red/green ratio were used to assess mitochondrial cells and intact mitochondrial membrane potential (MMP). We performed quantitative real-time polymerase chain reaction and Western blotting analyses of autophagy and mitophagy-related markers, including HIF1α, ATG5, pBECN1, BECN1, BAX, BNIP3L, DAPK1, and PINK1. Finally, FACS analysis with specific fluorescence-conjugated antibodies was performed to evaluate the potential cellular origin of CSF mitochondrial cells. Twenty-seven females (62.8%) with a mean age of 47.4 ± 9.7 years were included in the study. Among 43 patients with hemorrhagic MMD, 23 (53.5%) had poor outcomes. The difference in MMP was evident between the two groups (2.4 ± 0.2 in patients with poor outcome vs. 3.5 ± 0.4 in patients with good outcome; p = 0.02). A significantly higher expression (2-ΔCt) of HIF1α, ATG5, DAPK1 followed by BAX and BNIP3L mRNA and protein was also observed in poor-outcome patients compared to those with good outcomes. Higher percentage of vWF-positive mitochondria, suggesting endothelial cell origins, was observed in patients with good outcome compared with those with poor outcome (25.0 ± 1.4% in patients with good outcome vs. 17.5 ± 1.5% in those with poor outcome; p < 0.01). We observed the association between increased mitochondrial dysfunction concomitant with autophagy and mitophagy in CSF cells and neurological outcomes in adult patients with hemorrhagic MMD. Further prospective multicenter studies are needed to determine whether it has a diagnostic value for risk prediction.

Project description:BackgroundCerebrospinal fluid (CSF) biomarkers are increasingly being used to support a diagnosis of Alzheimer's disease (AD). Their clinical utility for differentiating AD from non-AD neurodegenerative dementias, such as dementia with Lewy bodies (DLB) or frontotemporal dementia (FTD), is less well established. We aimed to determine the diagnostic utility of an extended panel of CSF biomarkers to differentiate AD from a range of other neurodegenerative dementias.MethodsWe used immunoassays to measure conventional CSF markers of amyloid and tau pathology (amyloid beta (Aβ)1-42, total tau (T-tau), and phosphorylated tau (P-tau)) as well as amyloid processing (AβX-38, AβX-40, AβX-42, soluble amyloid precursor protein (sAPP)α, and sAPPβ), large fibre axonal degeneration (neurofilament light chain (NFL)), and neuroinflammation (YKL-40) in 245 patients with a variety of dementias and 30 controls. Patients fulfilled consensus criteria for AD (n = 156), DLB (n = 20), behavioural variant frontotemporal dementia (bvFTD; n = 45), progressive non-fluent aphasia (PNFA; n = 17), and semantic dementia (SD; n = 7); approximately 10% were pathology/genetically confirmed (n = 26). Global tests based on generalised least squares regression were used to determine differences between groups. Non-parametric receiver operating characteristic (ROC) curves and area under the curve (AUC) analyses were used to quantify how well each biomarker discriminated AD from each of the other diagnostic groups (or combinations of groups). CSF cut-points for the major biomarkers found to have diagnostic utility were validated using an independent cohort which included causes of AD (n = 104), DLB (n = 5), bvFTD (n = 12), PNFA (n = 3), SD (n = 9), and controls (n = 10).ResultsThere were significant global differences in Aβ1-42, T-tau, T-tau/Aβ1-42 ratio, P-tau-181, NFL, AβX-42, AβX-42/X-40 ratio, APPα, and APPβ between groups. At a fixed sensitivity of 85%, AβX-42/X-40 could differentiate AD from controls, bvFTD, and SD with specificities of 93%, 85%, and 100%, respectively; for T-tau/Aβ1-42 these specificities were 83%, 70%, and 86%. AβX-42/X-40 had similar or higher specificity than Aβ1-42. No biomarker or ratio could differentiate AD from DLB or PNFA with specificity > 50%. Similar sensitivities and specificities were found in the independent validation cohort for differentiating AD and other dementias and in a pathology/genetically confirmed sub-cohort.ConclusionsCSF AβX-42/X-40 and T-tau/Aβ1-42 ratios have utility in distinguishing AD from controls, bvFTD, and SD. None of the biomarkers tested had good specificity at distinguishing AD from DLB or PNFA.

Dataset Information

A Panel of Exosome-Derived miRNAs of Cerebrospinal Fluid for the Diagnosis of Moyamoya Disease.

Publications

A Panel of Exosome-Derived miRNAs of Cerebrospinal Fluid for the Diagnosis of Moyamoya Disease.

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