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

Giuliani, Angelica; Gaetani, Simona; Sorgentoni, Giulia; Agarbati, Silvia; Laggetta, Maristella; Matacchione, Giulia; Gobbi, Mirko; Rossi, Tommaso; Galeazzi, Roberta; Piccinini, Giulia; Pelliccioni, Giuseppe; Bonfigli, Anna Rita; Procopio, Antonio Domenico; Albertini, Maria Cristina; Olivieri, Fabiola; Fazioli, Francesca

doi:10.3389/fnagi.2021.647015

Cited by 29 publications

(16 citation statements)

References 60 publications

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“…Therefore, serum miR-146a-5p level may be a circulating marker of the efficacy of the anti-inflammatory response and thus of the susceptibility to develop complications. Consistent with this, miR-146a-5p is a well-established marker of inflammation and is associated with a variety of immune and non-immune inflammatory conditions [ 14 , 43 – 45 ], including CVD, Alzheimer’s disease, and type 2 diabetes [ 34 , 46 – 49 ].…”

Section: Discussionmentioning

confidence: 76%

MicroRNA 146a is associated with diabetic complications in type 1 diabetic patients from the EURODIAB PCS

et al. 2021

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Background MicroRNA-146a-5p (miR-146a-5p) is a key regulator of inflammatory processes. Expression of miR-146a-5p is altered in target organs of diabetic complications and deficiency of miR-146a-5p has been implicated in their pathogenesis. We investigated if serum miR-146a-5p levels were independently associated with micro/macrovascular complications of type 1 diabetes (DM1). Methods A nested case–control study from the EURODIAB PCS of 447 DM1 patients was performed. Cases (n = 294) had one or more complications of diabetes, whereas controls (n = 153) did not have any complication. Total RNA was isolated from all subjects and miR-146a-5p levels measured by qPCR. Both the endogenous controls U6 snRNA and the spike (Cel-miR-39) were used to normalize the results. Logistic regression analysis was carried out to investigate the association of miR-146a-5p with diabetes complications. Results MiR-146a-5p levels were significantly lower in cases [1.15 (0.32–3.34)] compared to controls [1.74 (0.44–6.74) P = 0.039]. Logistic regression analysis showed that levels of miR-146a-5p in the upper quartile were inversely associated with reduced odds ratio (OR) of all complications (OR 0.34 [95% CI 0.14–0.76]) and particularly with cardiovascular diseases (CVD) (OR 0.31 [95% CI 0.11–0.84]) and diabetic retinopathy (OR 0.40 [95% CI 0.16–0.99]), independently of age, sex, diabetes duration, A1c, hypertension, AER, eGFR, NT-proBNP, and TNF-α. Conclusions In this large cohort of DM1 patients, we reported an inverse and independent association of miR-146a-5p with diabetes chronic complications and in particular with CVD and retinopathy, suggesting that miR-146a-5p may be a novel candidate biomarker of DM1 complications.

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Section: Discussionmentioning

confidence: 76%

MicroRNA 146a is associated with diabetic complications in type 1 diabetic patients from the EURODIAB PCS

et al. 2021

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“…For instance, AD patients were accurately distinguished from healthy controls based on the downregulation of miR-9-5p in whole-blood samples (Souza et al, 2020). Giuliani et al (2021) evaluated the plasma levels of miR-17-5p, miR-21-5p, and miR-126-3p in a cohort of AD patients and found that they were significantly upregulated compared to those of healthy controls. Additionally, cases of mild and severe cognitive impairment could also be discriminated based on the level of miR-126-3p expression (Giuliani et al, 2021).…”

Section: Inflamma-micrornas As Diagnostic Biomarkers For Alzheimer's Diseasementioning

confidence: 99%

“…Giuliani et al (2021) evaluated the plasma levels of miR-17-5p, miR-21-5p, and miR-126-3p in a cohort of AD patients and found that they were significantly upregulated compared to those of healthy controls. Additionally, cases of mild and severe cognitive impairment could also be discriminated based on the level of miR-126-3p expression (Giuliani et al, 2021). Moreover, analyses of the expression profile of inflamma-miRNAs demonstrated that plasma miR-34a and miR-146a levels, as well as CSF miR-34a, miR-125b, and miR-146a levels in AD patients were significantly lower than those in control subjects.…”

Section: Inflamma-micrornas As Diagnostic Biomarkers For Alzheimer's Diseasementioning

confidence: 99%

Inflamma-MicroRNAs in Alzheimer’s Disease: From Disease Pathogenesis to Therapeutic Potentials

Liang

Wang

2021

Front. Cell. Neurosci.

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Alzheimer’s disease (AD) is the most common cause of senile dementia. Although AD research has made important breakthroughs, the pathogenesis of this disease remains unclear, and specific AD diagnostic biomarkers and therapeutic strategies are still lacking. Recent studies have demonstrated that neuroinflammation is involved in AD pathogenesis and is closely related to other health effects. MicroRNAs (miRNAs) are a class of endogenous short sequence non-coding RNAs that indirectly inhibit translation or directly degrade messenger RNA (mRNA) by specifically binding to its 3′ untranslated region (UTR). Several broadly expressed miRNAs including miR-21, miR-146a, and miR-155, have now been shown to regulate microglia/astrocytes activation. Other miRNAs, including miR-126 and miR-132, show a progressive link to the neuroinflammatory signaling. Therefore, further studies on these inflamma-miRNAs may shed light on the pathological mechanisms of AD. The differential expression of inflamma-miRNAs (such as miR-29a, miR-125b, and miR-126-5p) in the peripheral circulation may respond to AD progression, similar to inflammation, and therefore may become potential diagnostic biomarkers for AD. Moreover, inflamma-miRNAs could also be promising therapeutic targets for AD treatment. This review provides insights into the role of inflamma-miRNAs in AD, as well as an overview of general inflamma-miRNA biology, their implications in pathophysiology, and their potential roles as biomarkers and therapeutic targets.

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“…MiR-21 can inhibit cell apoptosis induced by Aβ 1−42 via modulating cell death protein 4 (PDCD4) /phosphatidylinositol 3-kinase PI3K/AKT/GSK-3β pathway in the CNS (Feng et al, 2018 ). Meanwhile circulating miR-21-5p was significantly upregulated in the plasma of AD patients and was negatively correlated to cognitive impairment (Giuliani et al, 2021 ). Simultaneously, disturbed level of miR-21 was observed in diverse neuropathic pain models (Zhong et al, 2019 ) where it targets metalloproteinase-3 (TIMP3) and chemokines C-C motif ligand 1 (CCL1) that consequently evoke cytokine production of TNF-α, IL-1β, and IL-6 and aggravate neuroinflammation.…”

Section: Pain: the Underestimated Companion In Alzheimer's Disease?mentioning

confidence: 99%

MicroRNAs as Potential Orchestrators of Alzheimer's Disease-Related Pathologies: Insights on Current Status and Future Possibilities

Abuelezz

Nasr

Abdulkader

et al. 2021

Front. Aging Neurosci.

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Alzheimer's disease (AD) is a progressive and deleterious neurodegenerative disease, strongly affecting the cognitive functions and memory of seniors worldwide. Around 58% of the affected patients live in low and middle-income countries, with estimates of increasing deaths caused by AD in the coming decade. AD is a multifactor pathology. Mitochondrial function declines in AD brain and is currently emerging as a hallmark of this disease. It has been considered as one of the intracellular processes severely compromised in AD. Many mitochondrial parameters decline already during aging; mitochondrial efficiency for energy production, reactive oxygen species (ROS) metabolism and the de novo synthesis of pyrimidines, to reach an extensive functional failure, concomitant with the onset of neurodegenerative conditions. Besides its impact on cognitive functions, AD is characterized by loss of synapses, extracellular amyloid plaques composed of the amyloid-β peptide (Aβ), and intracellular aggregates of hyperphosphorylated Tau protein, accompanied by drastic sleep disorders, sensory function alterations and pain sensitization. Unfortunately, till date, effective management of AD-related disorders and early, non-invasive AD diagnostic markers are yet to be found. MicroRNAs (miRNAs) are small non-coding nucleic acids that regulate key signaling pathway(s) in various disease conditions. About 70% of experimentally detectable miRNAs are expressed in the brain where they regulate neurite outgrowth, dendritic spine morphology, and synaptic plasticity. Increasing studies suggest that miRNAs are intimately involved in synaptic function and specific signals during memory formation. This has been the pivotal key for considering miRNAs crucial molecules to be studied in AD. MicroRNAs dysfunctions are increasingly acknowledged as a pivotal contributor in AD via deregulating genes involved in AD pathogenesis. Moreover, miRNAs have been proved to control pain sensitization processes and regulate circadian clock system that affects the sleep process. Interestingly, the differential expression of miRNA panels implies their emerging potential as diagnostic AD biomarkers. In this review, we will present an updated analysis of miRNAs role in regulating signaling processes that are involved in AD-related pathologies. We will discuss the current challenges against wider use of miRNAs and the future promising capabilities of miRNAs as diagnostic and therapeutic means for better management of AD.

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

Cited by 29 publications

References 60 publications

MicroRNA 146a is associated with diabetic complications in type 1 diabetic patients from the EURODIAB PCS

MicroRNA 146a is associated with diabetic complications in type 1 diabetic patients from the EURODIAB PCS

Inflamma-MicroRNAs in Alzheimer’s Disease: From Disease Pathogenesis to Therapeutic Potentials

MicroRNAs as Potential Orchestrators of Alzheimer's Disease-Related Pathologies: Insights on Current Status and Future Possibilities

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