Extracellular vesicles and Alzheimer’s disease in the novel era of Precision Medicine: implications for disease progression, diagnosis and treatment

Gomes, Patrícia; Tzouanou, Foteini; Skolariki, Konstantina; Vamvaka-Iakovou, Anastasia; Noguera-Ortiz, Carlos; Tsirtsaki, Katerina; Waites, Clarissa L.; Vlamos, Panagiotis; Sousa, Nuno; Bruno, Claudio; Kapogiannis, Dimitrios; Sotiropoulos, Ioannis

doi:10.1016/j.expneurol.2022.114183

Cited by 22 publications

(21 citation statements)

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“…15% relative enrichment; a finding that is in agreement with previous studies supporting the presence of synaptic proteins in the exosome cargo and their potential use as biomarkers in disorders characterized by synaptic malfunction/loss e.g. Alzheimer's disease [9]. Western blot analysis of the EVs yield of the two methods confirmed the proteomic findings by detecting a higher abundance of EV markers (i.e., CD81, flotillin-1) and proteins such as EEA1, which are derived from the endolysosomal pathway, the origin of sEVs such as exosomes, in the release protocol (Fig.…”

Section: The Ev Fraction Of the Release Methods Is Enriched In Protei...supporting

confidence: 91%

“…Isolation and characterization of subpopulations of pure and physiologically relevant small EVs (sEVs) from the brain is of paramount importance for advancing our understanding of EV biology and its potential use for disease diagnosis, prognosis, and treatment [ 9 , 36 , 37 ]. Over the past 30 years, EVs have been successfully isolated from cell culture media and body fluids (e.g., CSF, blood, urine, sperm, breast milk), with specific precautions taken into account to decrease the interference from non-EVs structures [ 38 ].…”

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

“…8 Institute of Biosciences and Applications NCSR "Demokritos", Athens, Greece. 9 • thorough peer review by experienced researchers in your field…”

Section: Supplementary Informationmentioning

confidence: 99%

“…They can cross the blood–brain barrier to the periphery [ 6 , 7 ], where they can be harvested for their biomarker carrier capacity. Due to their intracellular origin, cargo protecting-abilities, and long half-lives, brain EVs reflect molecular processes in their originating cells, exhibiting great potential in diagnostics, treatment follow-up, and therapeutics for diverse neurological, neurodegenerative and psychiatric disorders, including brain cancer, multiple sclerosis, Alzheimer’s and Parkinson’s disease, major depression and schizophrenia [ 2 , 8 , 9 ]. Therefore, the collection of pure and physiologically relevant brain EVs, which constitute the gold-standard population against which peripheral EV biomarkers ought to be compared, is of the utmost importance.…”

Section: Introductionmentioning

confidence: 99%

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A novel isolation method for spontaneously released extracellular vesicles from brain tissue and its implications for stress-driven brain pathology

et al. 2023

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Background Extracellular vesicles (EVs), including small EVs (sEVs) such as exosomes, exhibit great potential for the diagnosis and treatment of brain disorders, representing a valuable tool for precision medicine. The latter demands high-quality human biospecimens, especially in complex disorders in which pathological and specimen heterogeneity, as well as diverse individual clinical profile, often complicate the development of precision therapeutic schemes and patient-tailored treatments. Thus, the collection and characterization of physiologically relevant sEVs are of the utmost importance. However, standard brain EV isolation approaches rely on tissue dissociation, which can contaminate EV fractions with intracellular vesicles. Methods Based on multiscale analytical platforms such as cryo-EM, label-free proteomics, advanced flow cytometry, and ExoView analyses, we compared and characterized the EV fraction isolated with this novel method with a classical digestion-based EV isolation procedure. Moreover, EV biogenesis was pharmacologically manipulated with either GW4869 or picrotoxin to assess the validity of the spontaneous-release method, while the injection of labelled-EVs into the mouse brain further supported the integrity of the isolated vesicles. Results We hereby present an efficient purification method that captures a sEV-enriched population spontaneously released by mouse and human brain tissue. In addition, we tested the significance of the release method under conditions where biogenesis/secretion of sEVs was pharmacologically manipulated, as well as under animals’ exposure to chronic stress, a clinically relevant precipitant of brain pathologies, such as depression and Alzheimer’s disease. Our findings show that the released method monitors the drug-evoked inhibition or enhancement of sEVs secretion while chronic stress induces the secretion of brain exosomes accompanied by memory loss and mood deficits suggesting a potential role of sEVs in the brain response to stress and related stress-driven brain pathology. Conclusions Overall, the spontaneous release method of sEV yield may contribute to the characterization and biomarker profile of physiologically relevant brain-derived sEVs in brain function and pathology.

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Section: The Ev Fraction Of the Release Methods Is Enriched In Protei...supporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

“…8 Institute of Biosciences and Applications NCSR "Demokritos", Athens, Greece. 9 • thorough peer review by experienced researchers in your field…”

Section: Supplementary Informationmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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A novel isolation method for spontaneously released extracellular vesicles from brain tissue and its implications for stress-driven brain pathology

et al. 2023

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Exosome nanovesicles: biomarkers and new strategies for treatment of human diseases

Xu,

Jiang,

et al. 2024

MedComm

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Exosomes are nanoscale vesicles of cellular origin. One of the main characteristics of exosomes is their ability to carry a wide range of biomolecules from their parental cells, which are important mediators of intercellular communication and play an important role in physiological and pathological processes. Exosomes have the advantages of biocompatibility, low immunogenicity, and wide biodistribution. As researchers’ understanding of exosomes has increased, various strategies have been proposed for their use in diagnosing and treating diseases. Here, we provide an overview of the biogenesis and composition of exosomes, describe the relationship between exosomes and disease progression, and focus on the use of exosomes as biomarkers for early screening, disease monitoring, and guiding therapy in refractory diseases such as tumors and neurodegenerative diseases. We also summarize the current applications of exosomes, especially engineered exosomes, for efficient drug delivery, targeted therapies, gene therapies, and immune vaccines. Finally, the current challenges and potential research directions for the clinical application of exosomes are also discussed. In conclusion, exosomes, as an emerging molecule that can be used in the diagnosis and treatment of diseases, combined with multidisciplinary innovative solutions, will play an important role in clinical applications.

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Subcellular proteomics insights into Alzheimer's disease development

Liang,

Zhuang,

Cao

et al. 2023

Proteomics Clinical Apps

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Alzheimer's disease (AD), one of the most common dementias, is a neurodegenerative disease characterized by cognitive impairment and decreased judgment function. The expected number of AD patient is increasing in the context of the world's advancing medical care and increasing human life expectancy. Since current molecular mechanism studies on AD pathogenesis are incomplete, there is no specific and effective therapeutic agent. Mass spectrometry (MS)‐based unbiased proteomics studies provide an effective and comprehensive approach. Many advances have been made in the study of the mechanism, diagnostic markers, and drug targets of AD using proteomics. This paper focus on subcellular level studies, reviews studies using proteomics to study AD‐associated mitochondrial dysfunction, synaptic, and myelin damage, the protein composition of amyloid plaques (APs) and neurofibrillary tangles (NFTs), changes in tissue extracellular vehicles (EVs) and exosome proteome, and the protein changes in ribosomes and lysosomes. The methods of sample separation and preparation and proteomic analysis as well as the main findings of these studies are involved. The results of these proteomics studies provide insights into the pathogenesis of AD and provide theoretical resource and direction for future research in AD, helping to identify new biomarkers and drugs targets for AD.

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Extracellular vesicles and Alzheimer’s disease in the novel era of Precision Medicine: implications for disease progression, diagnosis and treatment

Cited by 22 publications

References 255 publications

A novel isolation method for spontaneously released extracellular vesicles from brain tissue and its implications for stress-driven brain pathology

A novel isolation method for spontaneously released extracellular vesicles from brain tissue and its implications for stress-driven brain pathology

Exosome nanovesicles: biomarkers and new strategies for treatment of human diseases

Subcellular proteomics insights into Alzheimer's disease development

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