Quantification of brain-derived extracellular vesicles in plasma as a biomarker to diagnose Parkinson's and related diseases

Ohmichi, Takuma; Mitsuhashi, Masato; Tatebe, Harutsugu; Kasai, Takashi; El-Agnaf, Omar M. A.; Tokuda, Takahiko

doi:10.1016/j.parkreldis.2018.11.021

Cited by 95 publications

(80 citation statements)

References 27 publications

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“…These results were supported by ROC curve analysis on the compound marker, originated from the linear combination of all the differentially expressed EV markers, showing very high sensitivity and specificity for PD and MSA (AUC 0.908 and 0.974, respectively). Previous works have explored the utility of EVs as biomarkers for PD by quantifying brain-derived exosomes (AUC 0.75-0.82) 25 or by measuring specific target proteins like alpha-synuclein (αSyn) or DJ-1 in plasma neuronal-derived exosomes (AUC 0.654, 0.724). 26 The combination of multiple markers improved the diagnostic accuracy of neuronal-derived exosomes as shown by a recent work on quantification of both αSyn and clusterin differentiating PD from other proteinopathies and from MSA with high accuracy (AUC 0.98 and 0.94, respectively).…”

Section: Discussionmentioning

confidence: 99%

“…Previous reports have shown that the total number and size of EVs were not augmented in serum of PD, 28 whereas a more recent study demonstrated an increased number of plasmatic brain-derived EVs in PD. 25 Methodological factors such as isolation/extraction and quantification of EVs explain these differences. However, at the molecular level, it is recognized that endosome/lysosome pathway is a common defective pathway in sporadic and genetic PD, 29 and EVs are generated and secreted by the endosomal compartment called multivesicular bodies by fusion with plasma membrane.…”

Section: Discussionmentioning

confidence: 99%

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Immune profiling of plasma-derived extracellular vesicles identifies Parkinson disease

Vacchi

Burrello

Silvestre

et al. 2020

Neurol Neuroimmunol Neuroinflamm

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ObjectiveTo develop a diagnostic model based on plasma-derived extracellular vesicle (EV) subpopulations in Parkinson disease (PD) and atypical parkinsonism (AP), we applied an innovative flow cytometric multiplex bead-based platform.MethodsPlasma-derived EVs were isolated from PD, matched healthy controls, multiple system atrophy (MSA), and AP with tauopathies (AP-Tau). The expression levels of 37 EV surface markers were measured by flow cytometry and correlated with clinical scales. A diagnostic model based on EV surface markers expression was built via supervised machine learning algorithms and validated in an external cohort.ResultsDistinctive pools of EV surface markers related to inflammatory and immune cells stratified patients according to the clinical diagnosis. PD and MSA displayed a greater pool of overexpressed immune markers, suggesting a different immune dysregulation in PD and MSA vs AP-Tau. The receiver operating characteristic curve analysis of a compound EV marker showed optimal diagnostic performance for PD (area under the curve [AUC] 0.908; sensitivity 96.3%, specificity 78.9%) and MSA (AUC 0.974; sensitivity 100%, specificity 94.7%) and good accuracy for AP-Tau (AUC 0.718; sensitivity 77.8%, specificity 89.5%). A diagnostic model based on EV marker expression correctly classified 88.9% of patients with reliable diagnostic performance after internal and external validations.ConclusionsImmune profiling of plasmatic EVs represents a crucial step toward the identification of biomarkers of disease for PD and AP.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Immune profiling of plasma-derived extracellular vesicles identifies Parkinson disease

Vacchi

Burrello

Silvestre

et al. 2020

Neurol Neuroimmunol Neuroinflamm

View full text Add to dashboard Cite

show abstract

“…Within this context, in order to overcome the issue of specific EV-donor-cell identification, and to allow the distinction between neuron-, astrocyte-and oligodendrocyte-derived EVs, once isolated from plasma of PD patients, Ohmichi and colleagues in 2018 [189] generated an ELISA-based platform. The platform was able to successfully discriminate the three possible EV donors within the CNS, based on their specific expression of the common small EV marker CD81, coupled with either neuron-specific SNAP25 or astrocyte-specific EAAT1 or oligodendrocyte-specific OMG markers.…”

Section: 'Flipping the Table': Evs As Potential Novel Pd Biomarkersmentioning

confidence: 99%

Glia-Derived Extracellular Vesicles in Parkinson’s Disease

Marchetti

Leggio

L’Episcopo

et al. 2020

JCM

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Glial cells are fundamental players in the central nervous system (CNS) development and homeostasis, both in health and disease states. In Parkinson’s disease (PD), a dysfunctional glia-neuron crosstalk represents a common final pathway contributing to the chronic and progressive death of dopaminergic (DAergic) neurons of the substantia nigra pars compacta (SNpc). Notably, glial cells communicating with each other by an array of molecules, can acquire a “beneficial” or “destructive” phenotype, thereby enhancing neuronal death/vulnerability and/or exerting critical neuroprotective and neuroreparative functions, with mechanisms that are actively investigated. An important way of delivering messenger molecules within this glia-neuron cross-talk consists in the secretion of extracellular vesicles (EVs). EVs are nano-sized membranous particles able to convey a wide range of molecular cargoes in a controlled way, depending on the specific donor cell and the microenvironmental milieu. Given the dual role of glia in PD, glia-derived EVs may deliver molecules carrying various messages for the vulnerable/dysfunctional DAergic neurons. Here, we summarize the state-of-the-art of glial-neuron interactions and glia-derived EVs in PD. Also, EVs have the ability to cross the blood brain barrier (BBB), thus acting both within the CNS and outside, in the periphery. In these regards, this review discloses the emerging applications of EVs, with a special focus on glia-derived EVs as potential carriers of new biomarkers and nanotherapeutics for PD.

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“…Blo od plasma levels of exosomes derived from various sources such as neurons, astrocytes and oligodendrocytes were quantifi ed in diseased patients and healthy controls to formulate a correlation between the exosome levels and PD. Results showed that the plasma levels of neuron-derived exosomes (characterized using the biomarkers CD81 and SNAP25) were signifi cantly higher in PD compared to controls [45]. On an alysing the proteomic data of exosomes isolated from serum samples of PD patients, it was found that 23 proteins including Syntenin 1 were differentially abundant in Parkinson's patients [46].…”

Section: E Xosomes In Disease Diagnosticsmentioning

confidence: 99%

Molecular signatures in exosomes as diagnostic markers for neurodegenerative disorders

Rani¹,

Karthik²,

A³

2020

Ann Alzheimers Dement Care

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Exosomes are small membrane-bound entities of endocytic origin. These membrane-derived, extracellular vesicles have been shown to be secreted by a number of cell types such as adipocytes, platelets, cardiac progenitor cells, muscle cells, mesenchymal stem cells, lymphocytes, tumor cells, embryonic stem cells, umbilical cord blood-derived cells and cells in the central nervous system including neurons, neuroglial cells etc., These extracellular vesicles contain various protein, lipid, proinfl ammatory cytokines and RNA species whose content is altered under pathological diseased conditions of the CNS. Currently, the techniques available to diagnose neurodegenerative disorders involve analysing the physiological levels of certain proteins in the Cerebrospinal Fluid (CSF) and checking for extracellular senile plaque formation (protein aggregation and accumulation) in the brain using MRI/CT scans. These techniques are quite expensive, invasive and painful in nature as collecting the CSF and accessing the brain area are diffi cult. In the past few years, there is a growing interest on using exosomes for diagnosis of neurodegenerative disorders due to their easy availability from most of the biological fl uids including the blood, urine, saliva, breast milk, semen etc., their extremely high disease-specifi c bio-molecular signature/profi le, the ability of exosomes to cargo a variety of biomolecules in between cells and their capacity to cross the blood-brain barrier. These make them a potential biomarker for neurodegenerative disorder. This review begins with a brief introduction about exosomes and focuses mainly on using exosomes for diagnosing major neurodegenerative diseases like Prion disease, Amyotrophic lateral sclerosis, Huntington's disease, Parkinson's disease, and Alzheimer's disease.

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Quantification of brain-derived extracellular vesicles in plasma as a biomarker to diagnose Parkinson's and related diseases

Cited by 95 publications

References 27 publications

Immune profiling of plasma-derived extracellular vesicles identifies Parkinson disease

Immune profiling of plasma-derived extracellular vesicles identifies Parkinson disease

Glia-Derived Extracellular Vesicles in Parkinson’s Disease

Molecular signatures in exosomes as diagnostic markers for neurodegenerative disorders

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