Serum MicroRNA Profiles Serve as Novel Biomarkers for the Diagnosis of Alzheimer’s Disease

Dong, Hui; Li, Jialu; Huang, Lei; Chen, Xi; Li, Donghai; Wang, Tao; Hu, Chengping; Xu, Jun; Zhang, Chenyu; Zen, Ke; Xiao, Shifu; Qiao, Yan; Wang, Cheng

doi:10.1155/2015/625659

Cited by 170 publications

(118 citation statements)

References 43 publications

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“…Dong et al (2015) found that the expression of miR-93-5p in AD patients was 0.48 times that in control subjects, a finding consistent with those of the current study. Some studies have also reported the lower levels of miR-137, 181c, 9, 29a, and 29b in the serum of patients with mild cognitive impairment (Geekiyanage et al 2012).…”

Section: Discussionsupporting

confidence: 93%

Lower Serum Levels of miR-29c-3p and miR-19b-3p as Biomarkers for Alzheimer’s Disease

et al. 2017

Tohoku J. Exp. Med.

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MicroRNAs (miRNAs) are short noncoding RNA that participate in posttranscriptional gene regulation. However, little is understood about the roles of miRNAs in Alzheimer's disease (AD). In this study, we used next-generation sequencing on RNA extracted from the serum samples of 20 AD patients and 20 controls, yielding a total of 72 miRNAs with significantly changed expression levels. Among these candidates, we selected 9 miRNAs with most significant alteration in disease, and validated their expression levels using RT-qPCR analysis on serum samples from 45 AD patients and 40 control subjects. Thus, the serum levels of miR-146a-5p, 106b-3p, 195-5p, 20b-5p, and 497-5p were significantly higher, while those of miR-125b-3p, 29c-3p, 93-5p and 19b-3p were significantly lower in AD patients, compared with control subjects. Two miRNAs, miR-29c-3p and miR-19b-3p, were selected because both RNA deep-sequencing and q-PCR methods indicated lower serum levels of these miRNAs in AD patients. Computational analysis predicted that 3′-untranslated region of signal transduction and activator of transcription 3 (STAT3) mRNA is targeted both by miR-29c-3p and miR-19b-3p. Using SH-SY5Y human neuroblastoma cells, we showed that transfection with miR-29c-3p or miR-19b-3p inhibitor significantly increased STAT3 phosphorylation. Furthermore, Water maze test, which assesses the learning and memory deficits in rodents, showed that escape latency was significantly shorter in AD rats with overexpression of miR-29c-3p or miR-19b-3p than in control AD rats. These results suggest that miR-29c-3p or miR-19b-3p may contribute to the cognitive function. In conclusion, the serum levels of miR-29c-3p and miR-19b-3p are helpful biomarkers for AD.

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Section: Discussionsupporting

confidence: 93%

Lower Serum Levels of miR-29c-3p and miR-19b-3p as Biomarkers for Alzheimer’s Disease

et al. 2017

Tohoku J. Exp. Med.

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“…miR-9, miR-125b, and 146a were inversely expressed in CSF and serum/plasma samples from AD patients (Figure 3). Expression of miR-125b and 146a increased in the CSF and ECF serum samples from the AD patients while serum samples expression was downregulated [84–85,87,90]. Similarly, the up-regulation of miR-9 expression was common in CSF, ECF, and serum samples from AD patients.…”

Section: Critical Analysis and Discussion Of Circulatory Mirna Studiesmentioning

confidence: 99%

“…In studying the use of serum as a biofluid for the analysis of circulatory miRNAs, Dong et al, examined miRNA in the sera from AD patients, individuals with MCI and vascular dementia (VD), and non-demented controls [87]. Using Solexa sequencing and RT-qPCR analysis, Dong et al identified four miRNAs that were down-regulated in the AD patients but not in any other subject group: miR-31, miR-93, miR-143, and miR-146a.…”

Section: Circulatory Mirnas In Alzheimer’s Diseasementioning

confidence: 99%

“…However, these miRNAs levels did not distinguish MCI and VD patients from controls because only miR-93 and miR-146a were significantly elevated in MCI individuals compared to control subjects while, miR-143 was down-regulated, and miR-31 showed no change. In case of VD patients, miR-31, miR-93, and miR-146a were significantly up-regulated however miR-143 was downregulated [87]. Hence, difference in these miRNAs expression could be able to discriminate AD cases from control subjects, but not suitable to separate MCI and VD cases.…”

Section: Circulatory Mirnas In Alzheimer’s Diseasementioning

confidence: 99%

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Are circulating microRNAs peripheral biomarkers for Alzheimer's disease?

Kumar

Reddy

2016

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Diseas

248

181

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Alzheimer’s disease (AD) is a progressive neurodegenerative disease characterized by memory loss, multiple cognitive abnormalities and intellectual impairments. Currently, there are no drugs or agents that can delay and/or prevent the progression of disease in elderly individuals, and there are no peripheral biomarkers that can detect AD early in its pathogenesis. Research has focused on identifying biomarkers for AD so that treatment can be begun as soon as possible in order to restrict or prevent intellectual impairments, memory loss, and other cognitive abnormalities that are associated with the disease. One such potential biomarker is microRNAs that are found in circulatory biofluids, such as blood and blood components, serum and plasma. Blood and blood components are primary sources where miRNAs are released in either cell-free form and then bind to protein components, or are in an encapsulated form with microvesicle particles. Exosomal miRNAs are known to be stable in biofluids and can be detected by high throughput techniques, like microarray and RNA sequencing. In AD brain, enriched miRNAs encapsulated with exosomes crosses the blood brain barrier and secreted in the CSF and blood circulations. This review summarizes recent studies that have identified miRNAs in the blood, serum, plasma, exosomes, cerebral spinal fluids, and extracellular fluids as potential biomarkers of AD. Recent research has revealed only six miRNAs–miR-9, miR-125b, miR-146a, miR-181c, let-7g-5p, and miR-191-5p – that were reported by multiple investigators. Some studies analyzed the diagnostic potential of these six miRNAs through receiver operating curve analysis which indicates the significant area-under-curve values in different biofluid samples. miR-191-5p was found to have the maximum area-under-curve value (0.95) only in plasma and serum samples while smaller area-under-curve values were found for miR-125, miR-181c, miR-191-5p, miR-146a, and miR-9. This article shortlisted the promising miRNA candidates and discussed their diagnostic properties and cellular functions in order to search for potential biomarker for AD.

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“…The dysregulation of miRNAs is thought to be involved in many diseases, and changes in the miRNA expression profile have been observed in cerebral ischemia and AD. Studies have demonstrated that serum miRNAs miR-93, miR-146a, and miR-31 were significantly up regulated in VaD compared to the controls; thus, they could serve as specific biomarkers to discriminate AD from VaD [65]. Endogenous circulating miRNAs have been found to be stable and consistently detected in serum, plasma and other body fluids because of their packaging and secretion into the blood within exosomes.…”

Section: Peripheral Microrna (Mirna) Profiles As Novel Biomarkersmentioning

confidence: 99%

Post-stroke dementia – a comprehensive review

Mijajlović

Pavlović

Brainin

et al. 2017

BMC Med

532

411

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Post-stroke dementia (PSD) or post-stroke cognitive impairment (PSCI) may affect up to one third of stroke survivors. Various definitions of PSCI and PSD have been described. We propose PSD as a label for any dementia following stroke in temporal relation. Various tools are available to screen and assess cognition, with few PSD-specific instruments. Choice will depend on purpose of assessment, with differing instruments needed for brief screening (e.g., Montreal Cognitive Assessment) or diagnostic formulation (e.g., NINDS VCI battery). A comprehensive evaluation should include assessment of pre-stroke cognition (e.g., using Informant Questionnaire for Cognitive Decline in the Elderly), mood (e.g., using Hospital Anxiety and Depression Scale), and functional consequences of cognitive impairments (e.g., using modified Rankin Scale). A large number of biomarkers for PSD, including indicators for genetic polymorphisms, biomarkers in the cerebrospinal fluid and in the serum, inflammatory mediators, and peripheral microRNA profiles have been proposed. Currently, no specific biomarkers have been proven to robustly discriminate vulnerable patients (‘at risk brains’) from those with better prognosis or to discriminate Alzheimer’s disease dementia from PSD. Further, neuroimaging is an important diagnostic tool in PSD. The role of computerized tomography is limited to demonstrating type and location of the underlying primary lesion and indicating atrophy and severe white matter changes. Magnetic resonance imaging is the key neuroimaging modality and has high sensitivity and specificity for detecting pathological changes, including small vessel disease. Advanced multi-modal imaging includes diffusion tensor imaging for fiber tracking, by which changes in networks can be detected. Quantitative imaging of cerebral blood flow and metabolism by positron emission tomography can differentiate between vascular dementia and degenerative dementia and show the interaction between vascular and metabolic changes. Additionally, inflammatory changes after ischemia in the brain can be detected, which may play a role together with amyloid deposition in the development of PSD. Prevention of PSD can be achieved by prevention of stroke. As treatment strategies to inhibit the development and mitigate the course of PSD, lowering of blood pressure, statins, neuroprotective drugs, and anti-inflammatory agents have all been studied without convincing evidence of efficacy. Lifestyle interventions, physical activity, and cognitive training have been recently tested, but large controlled trials are still missing.

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Serum MicroRNA Profiles Serve as Novel Biomarkers for the Diagnosis of Alzheimer’s Disease

Cited by 170 publications

References 43 publications

Lower Serum Levels of miR-29c-3p and miR-19b-3p as Biomarkers for Alzheimer’s Disease

Lower Serum Levels of miR-29c-3p and miR-19b-3p as Biomarkers for Alzheimer’s Disease

Are circulating microRNAs peripheral biomarkers for Alzheimer's disease?

Post-stroke dementia – a comprehensive review

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