MicroRNA Expression Levels Are Altered in the Cerebrospinal Fluid of Patients with Young-Onset Alzheimer’s Disease

McKeever, Paul M.; Schneider, Raphaël; Taghdiri, Foad; Weichert, Anna; Multani, Namita; Brown, Robert A.; Boxer, Adam L.; Karydas, Anna; Miller, Bruce L.; Robertson, Janice; Tartaglia, Maria Carmela

doi:10.1007/s12035-018-1032-x

Cited by 145 publications

(130 citation statements)

References 121 publications

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“…Moreover, recent researches have shown that the dysregulation of microRNAs (miRNAs) may link to Aβ accumulation in AD patients as well as in MCI patients . It is also demonstrated that the abnormity of miRNAs such as miR‐144‐3p and let‐7g‐5p could be found in both MCI and AD patients, but very few evidence could verify the correlation between miRNAs and oxysterols in MCI patients.…”

Section: Introductionmentioning

confidence: 99%

27‐hydroxycholesterol promotes Aβ accumulation via altering Aβ metabolism in mild cognitive impairment patients and APP/PS1 mice

Zhang

et al. 2019

Brain Pathology

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The oxysterol 27-hydroxycholesterol (27-OHC) has been considered to play a key role in the pathogenesis of Alzheimer's disease (AD). Because β-amyloid peptide (Aβ) is the pathological hallmark of AD, the aim of this study is to verify whether 27-OHC could lead to cognitive impairment through modulating Aβ accumulation and deposition. Regulation of Aβ metabolism was explored as the pathogenic mechanism of 27-OHC. Furthermore, microRNAs (miRNAs) and their relations with 27-OHC were also detected. In present study, matched case-control study and APP/PS1 transgenic mice research were conducted. The results showed that the 27-OHC and Aβ in plasma were increased in mild cognitive impairment patients, and a slight correlation was found between 27-OHC and Aβ1-40. This relationship was also proved by the research of APP/PS1 mice. More severe learning and memory impairment and higher Aβ1-40 expression in brain and plasma were detected in the APP/PS1 mice of 27-OHC treatment group. In addition, increased amyloid plaques were also found in the hippocampus of 27-OHC-treated mice. In order to find out the mechanism of 27-OHC on regulating Aβ metabolism, the factors of Aβ production (APP, BACE1 and ADAM10), transport (LRP1 and RAGE) and elimination (NEP and IDE) were tested respectively. The gene and protein expressions of APP, BACE1 and RAGE were increased while LRP1 and IDE were decreased in the brain of 27-OHC-treated mice. At last, down-regulated expression of miRNA let-7g-5p was found after 27-OHC treatment. In conclusion, these findings suggested that excessive 27-OHC could enhance the accumulation and deposition of Aβ both in brain and blood, resulting in a severe impairment of cognition, especially in the modulation of Aβ1-40. The mechanism might be associated with the regulation of Aβ metabolism, and miRNA let-7g-5p was likely to play a vital role in this pathological process induced by 27-OHC.Brain Pathology 29 (2019) 558-573

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Section: Introductionmentioning

confidence: 99%

27‐hydroxycholesterol promotes Aβ accumulation via altering Aβ metabolism in mild cognitive impairment patients and APP/PS1 mice

Zhang

et al. 2019

Brain Pathology

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“…Researchers have also strived to distinguish between youngand late-onset AD (YOAD/LOAD). McKeever et al (2018) collected CSF samples from 17 YOAD patients, 13 LOAD patients, and 12 healthy controls; they found that CSF-derived ex-miR-125b-5p was increased in YOAD patients, whereas ex-miR-16-5p, ex-miR-451a, and ex-miR-605-5p were decreased. In addition, the altered levels of ex-miR-125b-5p, ex-miR-451a, and ex-miR-605-5p were similar in both LOAD and YOAD patients when compared with the healthy controls.…”

Section: Ex-mirnas As Biomarkers In Admentioning

confidence: 99%

Circulating Exosomal miRNA as Diagnostic Biomarkers of Neurodegenerative Diseases

Wang

Zhang

2020

Front. Mol. Neurosci.

115

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Neurodegenerative diseases (NDDs) are a group of diseases caused by chronic and progressive degeneration of neural tissue. The main pathological manifestations are neuronal degeneration and loss in the brain and/or spinal cord. Common NDDs include Alzheimer disease (AD), Parkinson disease (PD), Huntington disease (HD), and amyotrophic lateral sclerosis (ALS). The complicated pathological characteristics and different clinical manifestations of NDDs result in a lack of sensitive and efficient diagnostic methods. In addition, no sensitive biomarkers are available to monitor the course of NDDs, predict their prognosis, and monitor the therapeutic response. Despite extensive research in recent years, analysis of amyloid β (Aβ) and α-synuclein has failed to effectively improve NDD diagnosis. Although recent studies have indicated circulating miRNAs as promising diagnostic biomarkers of NDDs, the miRNA in the peripheral circulation is susceptible to interference by other components, making circulating miRNA results less consistent. Exosomes are small membrane vesicles with a diameter of approximately 30-100 nm that transport proteins, lipids, mRNA, and miRNA. Because recent studies have shown that exosomes have a double-membrane structure that can resist ribonuclease in the blood, giving exosomal miRNA high stability and making them resistant to degradation, they may become an ideal biomarker of circulating fluids. In this review, we discuss the applicability of circulating exosomal miRNAs as biomarkers, highlight the technical aspects of exosomal miRNA analysis, and review studies that have used circulating exosomal miRNAs as candidate diagnostic biomarkers of NDDs.

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“…It has been reported that alterations in CSF miRNAs can reflect the changes of miRNAs in brain pathological tissue better than those in blood or postmortem brain samples. 40 There are two reasons for this phenomenon: 41,42 (1) In view of the inherent limitations associated with obtaining brain tissue in vivo, most human studies use postmortem samples to study miRNA expression. However, the study of postmortem brain tissue may be confounded by an extended postmortem interval and prior medication exposure; (2) Peripheral blood may not closely reflect gene expression levels in the brain.…”

Section: Mirnas In Cerebrospinal Fluid (Csf) Examinationmentioning

confidence: 99%

<p>MicroRNA-Based Biomarkers in the Diagnosis and Monitoring of Therapeutic Response in Patients with Depression</p>

Xu¹,

Xia²,

Xia³

et al. 2019

NDT

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Depression is a debilitating mental illness that affects up to 120 million people worldwide; it is currently determined based on subjective diagnostic schemes that are limited by high uncertainty. Hence, there is an urgent need to identify effective and reliable biomarkers to increase diagnostic accuracy. MicroRNAs (miRNAs) constitute a recently discovered class of non-coding RNAs that play a key role in the regulation of gene expression by modulating translation, messenger RNA (mRNA) degradation, or stability of mRNA targets. Dysregulated expression of miRNAs is being investigated as a clinical biomarker for a variety of diseases, including depression. Accumulating evidence has shown that miRNAs participate in many aspects of neural plasticity, neurogenesis, and the stress response. This is supported by more direct studies based on human postmortem brain tissue that strongly indicate that miRNAs not only play a key role in the pathogenesis of major depressive disorder, but also present potential for the development of therapeutic targets. miRNAs in the peripheral and central nervous system are being considered as potential biomarkers in the diagnosis of depression and in monitoring the therapeutic response to antidepressants, owing to their stability, tissue-specificity, and disease-specific expression. In this review, we focus on various miRNAs in tissues and fluids that could be employed as diagnostic and therapeutic biomarkers in patients with depression.

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MicroRNA Expression Levels Are Altered in the Cerebrospinal Fluid of Patients with Young-Onset Alzheimer’s Disease

Cited by 145 publications

References 121 publications

27‐hydroxycholesterol promotes Aβ accumulation via altering Aβ metabolism in mild cognitive impairment patients and APP/PS1 mice

27‐hydroxycholesterol promotes Aβ accumulation via altering Aβ metabolism in mild cognitive impairment patients and APP/PS1 mice

Circulating Exosomal miRNA as Diagnostic Biomarkers of Neurodegenerative Diseases

<p>MicroRNA-Based Biomarkers in the Diagnosis and Monitoring of Therapeutic Response in Patients with Depression</p>

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