Validation of MicroRNA Biomarkers for Alzheimer’s Disease in Human Cerebrospinal Fluid

Wiedrick, Jack; Phillips, Jay I.; Lusardi, Theresa A.; McFarland, T.J.; Lind, Babett; Sandau, Ursula S.; Harrington, Christina A.; Lapidus, Jodi; Galasko, Douglas; Quinn, Joseph F.; Saugstad, Julie A.

doi:10.3233/jad-180539

Cited by 48 publications

(56 citation statements)

References 41 publications

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“…Numerous authors have investigated this opportunity in various medical fields. Evidence suggests that they could play an essential role as biomarkers in cancer through exosome-mediated intercellular communication [1,4,[52][53][54], in neurology for the diagnosis and prognosis of Alzheimer's disease [55], for patients with spinal cord injury [56], epilepsy [57] or neurodegenerative ailments [58]. It could also be used in other fields like cardiology, as a faster and more accurate means of diagnosis for acute cardiovascular disease or heart failure [59][60][61] and in the case of infectious diseases for the diagnosis of sepsis [62].…”

mentioning

confidence: 99%

miRNAs as Biomarkers in Disease: Latest Findings Regarding Their Role in Diagnosis and Prognosis

Condrat

Thompson

Barbu

et al. 2020

Cells

767

583

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MicroRNAs (miRNAs) represent a class of small, non-coding RNAs with the main roles of regulating mRNA through its degradation and adjusting protein levels. In recent years, extraordinary progress has been made in terms of identifying the origin and exact functions of miRNA, focusing on their potential use in both the research and the clinical field. This review aims at improving the current understanding of these molecules and their applicability in the medical field. A thorough analysis of the literature consulting resources available in online databases such as NCBI, PubMed, Medline, ScienceDirect, and UpToDate was performed. There is promising evidence that in spite of the lack of standardized protocols regarding the use of miRNAs in current clinical practice, they constitute a reliable tool for future use. These molecules meet most of the required criteria for being an ideal biomarker, such as accessibility, high specificity, and sensitivity. Despite present limitations, miRNAs as biomarkers for various conditions remain an impressive research field. As current techniques evolve, we anticipate that miRNAs will become a routine approach in the development of personalized patient profiles, thus permitting more specific therapeutic interventions.Biogenesis of miRNA begins in the nucleus, where the transcription of its precursor, primary miRNA or pri-miRNA takes place under the influence of RNA polymerases II and III [11,12]. The resulting molecule is a hairpin-like structure, which contains a loop at one end [11]. This primordial mi-RNA precursor that is usually made up of hundreds of nucleotides is then processed consecutively by two RNase III enzymes [13][14][15]. The first enzyme to act upon the pri-miRNA, which still resides in the nucleus, is called Drosha or DCGR8, and turns it into a new hairpin-like structure of approximately 70 nucleotides, the Precursor-miRNA or pre-miRNA. The latter is then transported to the cytoplasm, with the help of Exportin-5, where it is cleaved again by the Ago2/Dicer complex leading to the short, mature miRNA double strands [16].Further on, one of the strands, usually known as the guide strand, will be integrated into the RNA-induced silencing complex (RISC), while the other one, known as the passenger strand, is going to be degraded, even though in some occasions it has been found to be also functional [17]. In most cases, the strand that contains the less stable 5 end or a uracil at the beginning is more likely to be selected as the guide strand [18][19][20]. In those situations, where the passenger strand is not degraded and both get incorporated into the miRISC complex, the mature miRNA in the guide strand will be the dominant one [21,22].The main role of miRNA in the human body is gene regulation [23] by mediating the degradation of mRNA and also by regulating transcription and translation through canonical and non-canonical mechanisms [4]. The canonical mechanism means that the miRISC complex containing the miRNA guide strand is exerting its action by binding to the targ...

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mentioning

confidence: 99%

miRNAs as Biomarkers in Disease: Latest Findings Regarding Their Role in Diagnosis and Prognosis

Condrat

Thompson

Barbu

et al. 2020

Cells

767

583

View full text Add to dashboard Cite

show abstract

“…In this respect, miRNAs have several advantages over classical biomarkers. Several studies have shown that specific species of miRNAs detected in the biofluid of AD patients are consistent with the observed pathological changes (Keller et al, 2016;Swarbrick et al, 2019;Takousis et al, 2019;Wiedrick et al, 2019). MiRNAs in serum, plasma, or CSF show great stability when they are enwrapped in liposomes or bound to lipoproteins, which prevents their degradation and allows them to withstand severe environmental conditions (van den Berg et al, 2020).…”

Section: Mirnas Help With the Diagnosis Of Admentioning

confidence: 80%

MicroRNAs in Alzheimer’s Disease: Function and Potential Applications as Diagnostic Biomarkers

Wei

Wang

et al. 2020

Front. Mol. Neurosci.

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Alzheimer's disease (AD) is the most common form of dementia. Although the incidence of AD is high, the rates of diagnosis and treatment are relatively low. Moreover, effective means for the diagnosis and treatment of AD are still lacking. MicroRNAs (miRNAs, miRs) are non-coding RNAs that play regulatory roles by targeting mRNAs. The expression of miRNAs is conserved, temporal, and tissue-specific. Impairment of microRNA function is closely related to AD pathogenesis, including the betaamyloid and tau hallmarks of AD, and there is evidence that the expression of some microRNAs differs significantly between healthy people and AD patients. These properties of miRNAs endow them with potential diagnostic and therapeutic value in the treatment of this debilitating disease. This review provides comprehensive information about the regulatory function of miRNAs in AD, as well as potential applications as diagnostic biomarkers.

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“…In a multicenter validation study [152], it was reported that the measurement of miRNA in CSF can be biased by several pre-analytical and analytical sources of variability, which may produce inconsistent results. Previous studies using CSF from a relatively small number of subjects showed that several miRNAs were up-regulated or down-regulated in CSF of AD patients; however, the results were not consistent [152,153,154,155,156,157]. Therefore, the identification of confounding factors when analyzing miRNA in CSF is required.…”

Section: Biochemical Biomarkers For Early Diagnosis Of Alzheimer’smentioning

confidence: 99%

Extracellular Vesicle as a Source of Alzheimer’s Biomarkers: Opportunities and Challenges

Lee

Mankhong

Kang

2019

IJMS

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Alzheimer’s disease (AD) is a chronic progressive neurodegenerative disease characterized by memory decline and cognitive dysfunction. Although the primary causes of AD are not clear, it is widely accepted that the accumulation of amyloid beta (Aβ) and consecutive hyper-phosphorylation of tau, synaptic loss, oxidative stress and neuronal death might play a vital role in AD pathogenesis. Recently, it has been widely suggested that extracellular vesicles (EVs), which are released from virtually all cell types, are a mediator in regulating AD pathogenesis. Clinical evidence for the diagnostic performance of EV-associated biomarkers, particularly exosome biomarkers in the blood, is also emerging. In this review, we briefly introduce the biological function of EVs in the central nervous system and discuss the roles of EVs in AD pathogenesis. In particular, the roles of EVs associated with autophagy and lysosomal degradation systems in AD proteinopathy and in disease propagation are discussed. Next, we summarize candidates for biochemical AD biomarkers in EVs, including proteins and miRNAs. The accumulating data brings hope that the application of EVs will be helpful for early diagnostics and the identification of new therapeutic targets for AD. However, at the same time, there are several challenges in developing valid EV biomarkers. We highlight considerations for the development of AD biomarkers from circulating EVs, which includes the standardization of pre-analytical sources of variability, yield and purity of isolated EVs and quantification of EV biomarkers. The development of valid EV AD biomarkers may be facilitated by collaboration between investigators and the industry.

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Validation of MicroRNA Biomarkers for Alzheimer’s Disease in Human Cerebrospinal Fluid

Cited by 48 publications

References 41 publications

miRNAs as Biomarkers in Disease: Latest Findings Regarding Their Role in Diagnosis and Prognosis

miRNAs as Biomarkers in Disease: Latest Findings Regarding Their Role in Diagnosis and Prognosis

MicroRNAs in Alzheimer’s Disease: Function and Potential Applications as Diagnostic Biomarkers

Extracellular Vesicle as a Source of Alzheimer’s Biomarkers: Opportunities and Challenges

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