Genome-wide profiling and predicted significance of post-mortem brain microRNA in Alzheimer’s disease

Henriques, Adriane Dallanora; Machado-Silva, Wilcelly; Leite, Renata; Suemoto, Cláudia Kimie; Leite, Kátia Ramos Moreira; Srougi, Miguel; Pereira, Alexandre C.; Jacob‐Filho, Wilson; Nóbrega, Otávio de Tolêdo

doi:10.1016/j.mad.2020.111352

Cited by 27 publications

(21 citation statements)

References 93 publications

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“…From the top 15 dysregulated miRNA, miR-4449, miR-151a, miR-502, miR-652-5p, miR-16-1-3p, miR-136-3p, miR-20b-5p and miR-Let-7g-3p have been implicated in ageing, AD and other neurodegenerative diseases. For instance, miR-4449 is significantly downregulated in superior and middle temporal gyrus extracts of AD cases [ 25 ], and even though the current study showed upregulation of this miRNA, its expression could vary depending on the tissue under study. Upregulation of miR-151a circulating levels is also observed in AD and ischaemic stroke patients [ 26 , 27 ] and has a role in the strengthening of the endothelial cell barrier in primary lung endothelial cells [ 28 ], suggesting it could also impact the BBB.…”

Section: Discussionmentioning

confidence: 86%

RNA-Seq Profiling of Neutrophil-Derived Microvesicles in Alzheimer’s Disease Patients Identifies a miRNA Signature That May Impact Blood–Brain Barrier Integrity

Vázquez-Villaseñor

Smith

Thang

et al. 2022

IJMS

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(1) Background: Systemic infection is associated with increased neuroinflammation and accelerated cognitive decline in AD patients. Activated neutrophils produce neutrophil-derived microvesicles (NMV), which are internalised by human brain microvascular endothelial cells and increase their permeability in vitro, suggesting that NMV play a role in blood–brain barrier (BBB) integrity during infection. The current study investigated whether microRNA content of NMV from AD patients is significantly different compared to healthy controls and could impact cerebrovascular integrity. (2) Methods: Neutrophils isolated from peripheral blood samples of five AD and five healthy control donors without systemic infection were stimulated to produce NMV. MicroRNAs isolated from NMV were analysed by RNA-Seq, and online bioinformatic tools were used to identify significantly differentially expressed microRNAs in the NMV. Target and pathway analyses were performed to predict the impact of the candidate microRNAs on vascular integrity. (3) Results: There was no significant difference in either the number of neutrophils (p = 0.309) or the number of NMV (p = 0.3434) isolated from AD donors compared to control. However, 158 microRNAs were significantly dysregulated in AD NMV compared to controls, some of which were associated with BBB dysfunction, including miR-210, miR-20b-5p and miR-126-5p. Pathway analysis revealed numerous significantly affected pathways involved in regulating vascular integrity, including the TGFβ and PDGFB pathways, as well as Hippo, IL-2 and DNA damage signalling. (4) Conclusions: NMV from AD patients contain miRNAs that may alter the integrity of the BBB and represent a novel neutrophil-mediated mechanism for BBB dysfunction in AD and the accelerated cognitive decline seen as a result of a systemic infection.

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Section: Discussionmentioning

confidence: 86%

RNA-Seq Profiling of Neutrophil-Derived Microvesicles in Alzheimer’s Disease Patients Identifies a miRNA Signature That May Impact Blood–Brain Barrier Integrity

Vázquez-Villaseñor

Smith

Thang

et al. 2022

IJMS

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“…In recent years, microRNAs (miRNAs, miRs), endogenous short non-coding single-stranded RNA molecules, emerged as cost-effective biomarkers for the diagnosis of various human ARDs, including AD. Several studies identified specific miRNAs differentially expressed in postmortem brain tissues of AD patients (Clement et al, 2016;Henriques et al, 2020;Wingo et al, 2020). Since they can be also actively secreted by living cells in all body fluids as mediators of epigenetic information, miRNAs have been investigated also in cerebrospinal fluid (CSF; Marchegiani et al, 2019;Kumar and Reddy, 2021), as well as in plasma/serum of AD patients (Leidinger et al, 2013;Kumar et al, 2017;Mengel-From et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

Circulating Inflamma-miRs as Potential Biomarkers of Cognitive Impairment in Patients Affected by Alzheimer’s Disease

Giuliani

Gaetani

Sorgentoni

et al. 2021

Front. Aging Neurosci.

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Alzheimer’s disease (AD), the most prevalent neurodegenerative disease in the growing population of elderly people, is still lacking minimally-invasive circulating biomarkers that could facilitate the diagnosis and the monitoring of disease progression. MicroRNAs (miRNAs) are emerging as tissue-specific and/or circulating biomarkers of several age-related diseases, but evidence on AD is still not conclusive. Since a systemic pro-inflammatory status was associated with an increased risk of AD development and progression, we focused our investigation on a subset of miRNAs modulating the inflammatory process, namely inflamma-miRNAs. The expression of inflamma-miR-17-5p, -21-5p, -126-3p, and -146a-5p was analyzed in plasma samples from 116 patients with AD compared with 41 age-matched healthy control (HC) subjects. MiR-17-5p, miR-21-5p, and miR-126-3p plasma levels were significantly increased in AD patients compared to HC. Importantly, a strong inverse relationship was observed between miR-21-5p and miR-126-3p, and the cognitive impairment, assessed by Mini-Mental State Examination (MMSE). Notably, miR-126-3p was able to discriminate between mild and severe cognitive impairment. Overall, our results reinforce the hypothesis that circulating inflamma-miRNAs could be assessed as minimally invasive tools associated with the development and progression of cognitive impairment in AD.

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“…miRNA is a class of small noncoding single-stranded RNA with a length of 21∼23 nucleotides. It is widely found in various living organisms and plays an important role in the growth, development, and aging of living organisms [6, 7]. In clinical studies on miRNAs in AD, scholars have found abnormal expression of several miRNAs in peripheral blood or cerebrospinal fluid samples from AD patients [6].…”

Section: Introductionmentioning

confidence: 99%

“…It is widely found in various living organisms and plays an important role in the growth, development, and aging of living organisms [6, 7]. In clinical studies on miRNAs in AD, scholars have found abnormal expression of several miRNAs in peripheral blood or cerebrospinal fluid samples from AD patients [6]. For example, Adriane D et al [6] used a high-throughput microarray platform and microarray technology to study the expression changes of miRNAs in patients with AD, and 6 miRNAs were identified to be aberrantly expressed in the temporal gyrus of patients.…”

Section: Introductionmentioning

confidence: 99%

“…In clinical studies on miRNAs in AD, scholars have found abnormal expression of several miRNAs in peripheral blood or cerebrospinal fluid samples from AD patients [6]. For example, Adriane D et al [6] used a high-throughput microarray platform and microarray technology to study the expression changes of miRNAs in patients with AD, and 6 miRNAs were identified to be aberrantly expressed in the temporal gyrus of patients. Also, in the basic experimental study, similar changes of miRNAs have been observed in AD mice or cell models, such as miR-331-3p and miR-155 [7, 8].…”

Section: Introductionmentioning

confidence: 99%

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Differential Expression of miR-381-3p in Alzheimer’s Disease Patients and Its Role in Beta-Amyloid-Induced Neurotoxicity and Inflammation

Zhang

Liu

Teng

et al. 2021

Neuroimmunomodulation

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Introduction: This study aimed to explore the diagnostic value and effect of miR-381-3p on Alzheimer’s disease (AD). Methods: RT-qPCR was used for the measurement of miR-381-3p levels. Pearson correlation coefficient was used for the correlation analysis. Receiver operating characteristic (ROC) curve was constructed to assess the distinct ability of miR-381-3p for AD. SH-SY5Y cells were treated with Aβ25-35 to establish an AD cell model. The role of miR-381-3p on cell proliferation and apoptosis was detected. ELISA was applied to detect the protein levels of inﬂammatory cytokine expression. The target relationship of miR-381-3p with PTGS2 was verified by luciferase reporter gene assay. Results: Low expression of miR-381-3p was detected in the serum of AD patients and cell models. There was a negative association of serum miR-381-3p with the serum inflammatory cytokines. The ROC curve demonstrated the distinct ability of serum miR-381-3p for AD, with the AUC value of 0.898, with a sensitivity of 87.5%, and a specificity of 77.7%. Overexpression of miR-381-3p reversed the influence of Aβ25-35 on cell proliferation and apoptosis, but miR-381-3p downregulation exacerbated the influence. miR-381-3p overexpression inhibited the release of IL-6, IL-1β, and TNF-α induced by Aβ25-35 treatment, whereas miR-381-3p downregulation further promoted the release of inflammatory cytokines. PTGS2 was the target gene of miR-381-3p and was upregulated in AD cell models. Conclusion: miR-381-3p is less expressed in the serum of AD patients and has potential diagnostic values for AD. Overexpression of miR-381-3p may attenuate Aβ25-35-induced neurotoxicity and inflammatory responses via targeting PTGS2 in SH-SY5Y cells.

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Genome-wide profiling and predicted significance of post-mortem brain microRNA in Alzheimer’s disease

Cited by 27 publications

References 93 publications

RNA-Seq Profiling of Neutrophil-Derived Microvesicles in Alzheimer’s Disease Patients Identifies a miRNA Signature That May Impact Blood–Brain Barrier Integrity

RNA-Seq Profiling of Neutrophil-Derived Microvesicles in Alzheimer’s Disease Patients Identifies a miRNA Signature That May Impact Blood–Brain Barrier Integrity

Circulating Inflamma-miRs as Potential Biomarkers of Cognitive Impairment in Patients Affected by Alzheimer’s Disease

Differential Expression of miR-381-3p in Alzheimer’s Disease Patients and Its Role in Beta-Amyloid-Induced Neurotoxicity and Inflammation

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