Serum microRNA miR-501-3p as a potential biomarker related to the progression of Alzheimer's disease (original) (raw)
Related papers
2021
Background: There is an urgent need for non-invasive, cost-effective biomarkers for Alzheimer’s disease (AD), such as blood-based biomarkers. It is not only to support clinical diagnosis of dementia, but also to allow for timely pharmacological and non-pharmacological interventions evaluation. The aim of this study is to identify and validate a novel blood-based microRNA (miRNA) biomarker for dementia of Alzheimer’s disease type (DAT). The miRNA correlations with AD pathology and AD clinical-radiological imaging were conducted.Methods: We conducted miRNA-sequencing (miRNA-Seq) using peripheral blood mononuclear cells (PBMCs) isolated from a discovery cohort comprising DAT, mild cognitive impairment (MCI), and healthy subject (HS). Identified miRNA was validated in an independent cohort. Correlation analysis evaluated the relationships between miRNA expression and DAT clinical measures, including Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) scores, CS...
Blood serum miRNA: Non-invasive biomarkers for Alzheimer's disease
Experimental Neurology, 2012
There is an urgent need to identify non-invasive biomarkers for the detection of sporadic Alzheimer's disease (AD). We previously studied microRNAs (miRNAs) in AD autopsy brain samples and reported a connection between miR-137,-181c,-9,-29a/b and AD, through the regulation of ceramides. In this study, the potential role of these miRNAs as diagnostic markers for AD was investigated. We identified that these miRNAs were down-regulated in the blood serum of probable AD patients. The levels of these miRNAs were also reduced in the serum of AD risk factor models. Although the ability of these miRNAs to conclusively diagnose for AD is currently unknown, our findings suggest a potential use for circulating miRNAs, along with other markers, as non-invasive and relatively inexpensive biomarkers for the early diagnosis of AD, however, with further research and validation.
Oncotarget, 2017
Alzheimer's disease (AD) is the most common age-related dementia. Among its major challenges is identifying molecular signatures characteristic for the early AD stage in patients with Mild Cognitive Impairment (MCI-AD), which could serve for deciphering the AD pathomechanism and also as non-invasive, easy-to-access biomarkers. Using qRT-PCR we compared the microRNA (miRNA) profiles in blood plasma of 15 MCI-AD patients, whose diagnoses were confirmed by cerebrospinal fluid (CSF) biomarkers, with 20 AD patients and 15 non-demented, age-matched individuals (CTR).To minimize methodological variability, we adhered to standardization of blood and CSF assays recommended by the international Joint Programming for Neurodegenerative Diseases (JPND) BIOMARKAPD consortium, and we employed commercially available Exiqon qRT-PCR-assays. In the first screening, we assessed 179 miRNAs of plasma. We confirmed 23 miRNAs reported earlier as AD biomarker candidates in blood and found 26 novel diffe...
Systematic Review of miRNA as Biomarkers in Alzheimer’s Disease
Molecular Neurobiology, 2019
Currently there are 850,000 people with Alzheimer's disease in the UK, with an estimated rise to 1.1 million by 2025. Alzheimer's disease is characterised by the accumulation of amyloid-beta plaques and hyperphosphorylated tau in the brain causing a progressive decline in cognitive impairment. Small non-coding microRNA (miRNA) sequences have been found to be deregulated in the peripheral blood of Alzheimer patients. A systematic review was conducted to extract all miRNA found to be significantly deregulated in the peripheral blood. These deregulated miRNAs were cross-referenced against the miRNAs deregulated in the brain at Braak Stage III. This resulted in a panel of 10 miRNAs (hsa-mir-107, hsa-mir-26b, hsa-mir-30e, hsa-mir-34a, hsa-mir-485, hsa-mir200c, hsa-mir-210, hsa-mir-146a, hsa-mir-34c, and hsa-mir-125b) hypothesised to be deregulated early in Alzheimer's disease, nearly 20 years before the onset of clinical symptoms. After network analysis of the 10 miRNAs, they were found to be associated with the immune system, cell cycle, gene expression, cellular response to stress, neuron growth factor signalling, wnt signalling, cellular senescence, and Rho GTPases.
A blood based 12-miRNA signature of Alzheimer disease patients
Genome Biology, 2013
Background: Alzheimer disease (AD) is the most common form of dementia but the identification of reliable, early and non-invasive biomarkers remains a major challenge. We present a novel miRNA-based signature for detecting AD from blood samples.
Potential of hsa-miR200a-3p and hsa-miR502-3p as blood-based biomarker for Alzheimer's disease
Alzheimer's disease (AD) is one of the most important known dementia which affects thousands of people every year. Many factors are involved in this process, such as aberrant expression of miRNAs. Firstly, we analyzed two microarray datasets related to AD (GSE48552, GSE129053) to identify the differentially expressed miRNAs, and two miRNAs were selected for further validation. Dataset analysis showed that the expression of hsa-miR200a-3p and hsa-miR502-3p were up-regulated in AD. These findings were validated in plasma samples by qRT-PCR. ROC curve analysis showed that plasma levels of both miRNAs might discriminate the AD and healthy controls. In addition, in silico analysis revealed that the upregulation of these miRNAs could promote AD progression via affecting the expression of target molecules mainly ATF6 and dynactin. Totally, hsa-miR200a-3p and hsa-miR502-3p are upregulated in AD and their plasma levels can discriminate AD and healthy people, highlighting their potential ...
İstanbul tıp fakültesi dergisi, 2021
Objective: Inflammation and associated microRNAs (miRNA) both play essential roles in the pathogenesis of Alzheimer's disease (AD). The expression profile of miRNA's in an AD brain, also reflected in the peripheral blood mononuclear cells, may give support to the inflammatory changes seen in the course of AD. We aimed to investigate the expression levels of specific inflammatory miRNAs (mir-146a, mir-144, mir-34a) in both blood leukocytes and plasma of AD patients and to evaluate their potential usability as biomarkers in AD diagnosis and to also demonstrate whether the expression of these miRNAs differ between early and late-onset AD patients. Methods: We investigated the expression levels of miRNAs in 16 early-onset and 26 late-onset AD patients and in their respective controls by using qRT-PCR. Results: Plasma mir-144 levels were significantly different between EOAD and LOAD patients (p=0.015). In addition, levels of leukocyte mir-34a were significantly down-regulated in EOAD compared to LOAD patients (p=0.027). Our results also showed significant positive correlations between age and plasma mir-144 and leukocyte mir-34a expressions.
OMICS: A Journal of Integrative Biology, 2016
Alzheimer's disease (AD) is a progressive neurodegenerative disorder and the most common form of dementia. However, biomarkers that require testing in the brain tissue pose a formidable practical barrier to AD diagnostic innovation. MicroRNAs (miRNAs) are responsible for control of gene expression at the posttranscriptional level and are essential for the function of neuronal networks and neuronal survival. miRNA expression can impact the regulation of APP (amyloid beta A4 precursor protein), PSEN1 (presenilin 1), PSEN2 (presenilin 2), and BACE1 (beta-secretase 1) genes in the brain that were previously implicated in AD pathophysiology. Little is known, however, on the extent to which peripheral tissue (e.g., whole blood) miRNA variation might offer clinical predictive value for AD. Moreover, few studies have examined multiple peripheral miRNA expression data at the same time. We report here, to the best of our knowledge, the first whole-blood-based and parallel study of seven miRNAs (hsa-miR-9-5p, hsa-miR-29a-3p, hsa-miR-106a-5p, hsa-miR-106b-5p, hsa-miR-107, hsa-miR-125a-3p, and hsa-miR-125b-5p) in relation to AD susceptibility. Notably, these miRNAs are situated ''upstream'' to the genes implicated in AD. We measured the whole-blood miRNA expression by a real-time polymerase chain reaction in a large study sample (n = 281), comprising patients with AD (n = 172) and healthy controls (n = 109). A reduction in whole-blood expression of hsa-miR-9-5p, hsa-miR-106a-5p, hsa-miR-106b-5p, and hsa-miR-107 was significantly associated with an increased risk of AD (p < 0.05). Notably, after receiver operating characteristics curve analyses, hsa-miR-106a-5p displayed, as a predictor variable, 93% specificity and 68% sensitivity. On the other hand, the expression of hsa-miR-29a-3p, hsa-miR-125a-3p, and hsa-miR-125b-5p was not significantly different between patients and controls (p > 0.05). In conclusion, these observations warrant replication in larger samples while making a contribution to translational research, precision medicine, and biomarker literatures, by expanding the current efforts for AD diagnostic innovation to the realm of epigenomic pathways such as miRNA expression variation among patients.
2019
Background: Peripheral blood microRNAs (miRNA) have been identified as potential biomarkers for Alzheimer’s disease (AD). Study results have generally been inconsistent and limited by sample heterogeneity. The aim of this study is to establish candidate blood miRNA biomarkers for AD by comparing differences in miRNA expression between participants with brain amyloid imaging defined AD and normal cognition. Methods: Blood RNA was extracted from a subset of participants from the Australian Imaging Biomarkers Lifestyle Study of Ageing cohort (AIBL) with brain amyloid imaging results. MiRNA profiling was performed using small RNA sequencing on 71 participants, comprising 40 AD with high brain amyloid burden on imaging (amyloid positive) and 31 cognitively normal controls with low brain amyloid burden (amyloid negative). Cross-sectional comparisons were made between groups to examine differential miRNA expression levels using Fisher’s exact tests. Replication of results was undertaken us...
MicroRNAs as Future Treatment Tools and Diagnostic Biomarkers in Alzheimer’s Disease
Alzheimer's Disease [Working Title], 2022
Alzheimer's disease (AD) is a neurodegenerative disorder and is considered to be the most common form of dementia. This disorder is characterized by the formation of amyloid β (Aβ) plaques, neurofibrillary tangles, and alterations in synaptic function, all of which cause memory loss and behavioral disturbances. Despite the high prevalence of AD, effective therapeutic and diagnostic tools remain unavailable. MicroRNAs (miRNAs, miRs) are regulatory non-coding RNAs that target mRNAs. MiRNAs are involved in the regulation of the expressions of APP and BACE1, Aβ clearance, and the formation of neuro-fibrillary tangles. Furthermore, there are evidences that show alteration in the expression of several miRs in AD. MicroRNA is emerging as a biomarker because they have high specificity and, efficiency, and can be detected in biological fluids such as cerebrospinal fluid, tear, urine, blood. Moreover, miRNAs may be acquired and measured easily by utilizing real-time PCR, next-generation sequencing, or microarray. These techniques are cost-effective in comparison with imaging techniques such as magnetic resonance imaging, positron emission tomography. These features make miRNAs viable therapeutic as well as diagnostic tools in the treatment of AD. This review covers the regulatory function of miRNAs in AD, as well as their prospective applications as diagnostic biomarkers.