Toward Exosome-Based Neuronal Diagnostic Devices

Yoo, Yong Kyoung; Lee, Junwoo; Kim, Hyungsuk; Hwang, Kyo Seon; Yoon, Dae Sung

doi:10.3390/mi9120634

Cited by 25 publications

(15 citation statements)

References 106 publications

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“…These studies demonstrate the potential of CNS-derived blood exosomes as a source of diagnostic, prognostic, and progression biomarkers for neurodegenerative diseases. In addition to blood products, exosomes obtained from other biofluids, such as CSF and saliva, also have been used for diagnostic purposes (Yoo et al, 2018;Cao et al, 2019). Obtaining saliva from patients is less invasive than obtaining blood and saliva is easier to process because it does not coagulate.…”

Section: Cns-derived Exosomes As a Source Of Biomarkers For Neurodegementioning

confidence: 99%

CNS-Derived Blood Exosomes as a Promising Source of Biomarkers: Opportunities and Challenges

Hornung

Dutta

Bitan

2020

Front. Mol. Neurosci.

167

159

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Eukaryotic cells release different types of extracellular vesicles (EVs) including exosomes, ectosomes, and microvesicles. Exosomes are nanovesicles, 30-200 nm in diameter, that carry cell-and cell-state-specific cargo of proteins, lipids, and nucleic acids, including mRNA and miRNA. Recent studies have shown that central nervous system (CNS)-derived exosomes may carry amyloidogenic proteins and facilitate their cell-to-cell transfer, thus playing a critical role in the progression of neurodegenerative diseases, such as tauopathies and synucleinopathies. CNS-derived exosomes also have been shown to cross the blood-brain-barrier into the bloodstream and therefore have drawn substantial attention as a source of biomarkers for various neurodegenerative diseases as they can be isolated via a minimally invasive blood draw and report on the biochemical status of the CNS. However, although isolating specific brain-cell-derived exosomes from the blood is theoretically simple and the approach has great promise, practical details are of crucial importance and may compromise the reproducibility and utility of this approach, especially when different laboratories use different protocols. In this review we discuss the role of exosomes in neurodegenerative diseases, the usefulness of CNS-derived blood exosomes as a source of biomarkers for these diseases, and practical challenges associated with the methodology of CNS-derived blood exosomes and subsequent biomarker analysis.

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Section: Cns-derived Exosomes As a Source Of Biomarkers For Neurodegementioning

confidence: 99%

CNS-Derived Blood Exosomes as a Promising Source of Biomarkers: Opportunities and Challenges

Hornung

Dutta

Bitan

2020

Front. Mol. Neurosci.

167

159

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“…Radiolabelled AS administration to mice brains has demonstrated that it can be readily transported to blood circulation, probably via exosome release through the blood brain barrier (BBB) [69,87]. Exosomes are small vesicles (~30-150 nm) of the endocytic pathway that can move from cells to the periphery, carrying the intracellular cargo into the body's circulation [88]. Hence, it is believed that exosomes originating from the brain circulate in plasma, and upon isolation their content will be reflective of the neuronal state [87].…”

Section: Bloodmentioning

confidence: 99%

The Future of Targeted Gene-Based Treatment Strategies and Biomarkers in Parkinson’s Disease

et al. 2020

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Biomarkers and disease-modifying therapies are both urgent unmet medical needs in the treatment of Parkinson’s disease (PD) and must be developed concurrently because of their interdependent relationship: biomarkers for the early detection of disease (i.e., prior to overt neurodegeneration) are necessary in order for patients to receive maximal therapeutic benefit and vice versa; disease-modifying therapies must become available for patients whose potential for disease diagnosis and prognosis can be predicted with biomarkers. This review provides an overview of the milestones achieved to date in the therapeutic strategy development of disease-modifying therapies and biomarkers for PD, with a focus on the most common and advanced genetically linked targets alpha-synuclein (SNCA), leucine-rich repeat kinase-2 (LRRK2) and glucocerebrosidase (GBA1). Furthermore, we discuss the convergence of the different pathways and the importance of patient stratification and how these advances may apply more broadly to idiopathic PD. The heterogeneity of PD poses a challenge for therapeutic and biomarker development, however, the one gene- one target approach has brought us closer than ever before to an unprecedented number of clinical trials and biomarker advancements.

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“…The substances present in exosomes are not easily digested by enzymes as they are protected by lipid membrane bilayers (9,10). due to their small size, exosomes can pass through the blood-brain barrier (BBB) freely (11)(12)(13). exosomes can be used as biomarkers for several neurodegenerative diseases, including Parkinson's disease and prion diseases (14)(15)(16).…”

Section: Introductionmentioning

confidence: 99%

Elevated plasma levels of exosomal BACE1‑AS combined with the volume and thickness of the right entorhinal cortex may serve as a biomarker for the detection of Alzheimer's disease

Wang

Bian

et al. 2020

Mol Med Rep

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long non-coding rna (lncrna) and exosomes are involved in the pathological process of alzheimer's disease (ad), the pathological changes of which are usually first observed in the entorhinal cortex and hippocampus. The aim of the present study was to determine whether the measurement of plasma exosomal lncrna combined with image data of the entorhinal cortex and hippocampus could be used as a biomarker of ad. a total of 72 patients with ad and 62 controls were recruited, and the expression levels of several lncrnas were assessed. of the recruited participants, 22 patients and 26 controls received brain 3d-BraVo sequence magnetic resonance imaging (Mri) scans, which were analyzed using an automated analysis tool. The plasma exosomal β-site amyloid precursor protein cleaving enzyme-1-antisense transcript (BACE1-AS) levels in patients with AD were significantly higher compared with the controls (P<0.005). receiver operating characteristic curve analysis revealed that the area under the curve (auc) was 0.761 for Bace1-aS, the sensitivity was 87.5%, and the specificity was 61.3%. Analysis of MRI images indicated that the right entorhinal cortex volume (P=0.015) and thickness (P= 0.022) in patients with AD were significantly smaller. The auc was 0.688 for the right entorhinal cortex volume, with a sensitivity of 59.1%, and the specificity was 84.6%. The auc was 0.689 for right entorhinal cortex thickness, with a sensitivity of 80.8%, and the specificity was 59.1%. a series-parallel test which integrated the Bace1-aS with the right entorhinal cortex volume and thickness, raised the specificity and sensitivity to 96.15 and 90.91%, respectively. a logistic regression model demonstrated that combination of the 3 indices provided improved sensitivity and specificity simultaneously, particularly when adjusting for age and sex (AUC, 0.819; sensitivity, 81%; specificity, 73.1%). The results of the present study demonstrated that detection of plasma exosomal Bace1-aS levels combined with the volume and thickness of the right entorhinal cortex may be used as a novel biomarker of ad.

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Toward Exosome-Based Neuronal Diagnostic Devices

Cited by 25 publications

References 106 publications

CNS-Derived Blood Exosomes as a Promising Source of Biomarkers: Opportunities and Challenges

CNS-Derived Blood Exosomes as a Promising Source of Biomarkers: Opportunities and Challenges

The Future of Targeted Gene-Based Treatment Strategies and Biomarkers in Parkinson’s Disease

Elevated plasma levels of exosomal BACE1‑AS combined with the volume and thickness of the right entorhinal cortex may serve as a biomarker for the detection of Alzheimer's disease

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