{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,21]],"date-time":"2026-02-21T06:04:47Z","timestamp":1771653887228,"version":"3.50.1"},"reference-count":148,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T00:00:00Z","timestamp":1771459200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Florida Department of Health Ed and Ethel Moore Alzheimer\u2019s Disease Research Program","award":["23A07"],"award-info":[{"award-number":["23A07"]}]},{"name":"Preeminent Postdoctoral Program"},{"name":"Office of Undergraduate Research"},{"name":"Learning Institute for Elders at the University of Central Florida (LIFE at UCF) Al Dallago"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Extracellular vesicles (EVs) are nanoscale membrane-enclosed vesicles that mediate intercellular communication and participate in both physiological and pathological signaling processes. Recent studies underscore the critical roles of EVs in the propagation of tau pathology and the diagnostic and therapeutic aspects of tauopathies, a class of neurodegenerative diseases marked by the pathological accumulation of the protein tau, contributing to cognitive decline and neuronal loss. This review aims to explore the many roles of EVs in tauopathies, emphasizing their ability to carry and transmit misfolded tau, modulate immune responses through microglial interactions, and serve as carriers of disease-specific biomarkers. We describe current findings on extravesicular tau, miRNAs, and mRNAs as diagnostic indicators in Alzheimer\u2019s disease and related tauopathies and evaluate the therapeutic potential of both endogenous and engineered EVs for delivering therapeutic agents or neuroprotective cargo. Challenges such as isolation standardization, cargo loading efficiency, and biodistribution are also discussed, along with potential strategies to overcome them. Overall, the evidence emphasizes EVs as key players in the pathophysiology, diagnosis, and treatment of tauopathies, offering a strong and compelling platform for precision medicine and clinical applications in the future.<\/jats:p>","DOI":"10.3390\/ijms27041998","type":"journal-article","created":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T15:57:29Z","timestamp":1771516649000},"page":"1998","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Extracellular Vesicles in Tauopathies: Mechanisms and Applications"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-2945-2126","authenticated-orcid":false,"given":"Varun","family":"Nannuri","sequence":"first","affiliation":[{"name":"Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, FL 32827, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ebaa","family":"Ababneh","sequence":"additional","affiliation":[{"name":"Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, FL 32827, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Serena","family":"El Rayes","sequence":"additional","affiliation":[{"name":"Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, FL 32827, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jonhoi","family":"Smith","sequence":"additional","affiliation":[{"name":"Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, FL 32827, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2788-5457","authenticated-orcid":false,"given":"Kiminobu","family":"Sugaya","sequence":"additional","affiliation":[{"name":"Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, FL 32827, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jihe","family":"Zhao","sequence":"additional","affiliation":[{"name":"Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, FL 32827, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e12404","DOI":"10.1002\/jev2.12404","article-title":"Minimal information for studies of extracellular vesicles (MISEV2023): From basic to advanced approaches","volume":"13","author":"Welsh","year":"2024","journal-title":"J. Extracell. Vesicles"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1016\/B978-0-323-98817-9.00015-6","article-title":"Chapter 12\u2014The tauopathies","volume":"Volume 196","author":"Younger","year":"2023","journal-title":"Handbook of Clinical Neurology"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1291","DOI":"10.1016\/j.mayocp.2017.04.016","article-title":"Current Understanding of Neurodegenerative Diseases Associated with the Protein Tau","volume":"92","author":"Josephs","year":"2017","journal-title":"Mayo Clin. Proc."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"444","DOI":"10.1093\/brain\/awad388","article-title":"Nigrostriatal tau pathology in parkinsonism and Parkinson\u2019s disease","volume":"147","author":"Chu","year":"2024","journal-title":"Brain"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"12445","DOI":"10.1074\/jbc.M115.709485","article-title":"Extracellular Vesicles Isolated from the Brains of rTg4510 Mice Seed Tau Protein Aggregation in a Threshold-dependent Manner","volume":"291","author":"Polanco","year":"2016","journal-title":"J. Biol. Chem."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1186\/s40478-018-0514-4","article-title":"Exosomes taken up by neurons hijack the endosomal pathway to spread to interconnected neurons","volume":"6","author":"Polanco","year":"2018","journal-title":"Acta Neuropathol. Commun."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1476","DOI":"10.1093\/brain\/awaa090","article-title":"Microglial exosomes facilitate \u03b1-synuclein transmission in Parkinson\u2019s disease","volume":"143","author":"Guo","year":"2020","journal-title":"Brain"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1792","DOI":"10.1016\/j.neurobiolaging.2014.02.012","article-title":"Exosome reduction in vivo is associated with lower amyloid plaque load in the 5XFAD mouse model of Alzheimer\u2019s disease","volume":"35","author":"Dinkins","year":"2014","journal-title":"Neurobiol. Aging"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1016\/j.freeradbiomed.2017.08.028","article-title":"Exosomal biomarkers in Down syndrome and Alzheimer\u2019s disease","volume":"114","author":"Hamlett","year":"2018","journal-title":"Free Radic. Biol. Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"360","DOI":"10.1016\/j.nbd.2011.01.029","article-title":"Lysosomal dysfunction increases exosome-mediated alpha-synuclein release and transmission","volume":"42","author":"Seow","year":"2011","journal-title":"Neurobiol. Dis."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"3058","DOI":"10.1093\/brain\/awac115","article-title":"Detection of neuron-derived pathological \u03b1-synuclein in blood","volume":"145","author":"Kluge","year":"2022","journal-title":"Brain"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"3842","DOI":"10.1074\/jbc.M111.277061","article-title":"Exosome-associated Tau Is Secreted in Tauopathy Models and Is Selectively Phosphorylated in Cerebrospinal Fluid in Early Alzheimer Disease","volume":"287","author":"Saman","year":"2012","journal-title":"J. Biol. Chem."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1125","DOI":"10.1016\/j.jalz.2016.04.003","article-title":"CNS tau efflux via exosomes is likely increased in Parkinson\u2019s disease but not in Alzheimer\u2019s disease","volume":"12","author":"Shi","year":"2016","journal-title":"Alzheimers Dement."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1584","DOI":"10.1038\/nn.4132","article-title":"Depletion of microglia and inhibition of exosome synthesis halt tau propagation","volume":"18","author":"Asai","year":"2015","journal-title":"Nat. Neurosci."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"652","DOI":"10.1186\/s12967-023-04461-4","article-title":"FTO-targeted siRNA delivery by MSC-derived exosomes synergistically alleviates dopaminergic neuronal death in Parkinson\u2019s disease via m6A-dependent regulation of ATM mRNA","volume":"21","author":"Geng","year":"2023","journal-title":"J. Transl. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"404","DOI":"10.1038\/s41392-023-01657-4","article-title":"Fe65-engineered neuronal exosomes encapsulating corynoxine-B ameliorate cognition and pathology of Alzheimer\u2019s disease","volume":"8","author":"Iyaswamy","year":"2023","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1038\/nbt.1807","article-title":"Delivery of siRNA to the mouse brain by systemic injection of targeted exosomes","volume":"29","author":"Seow","year":"2011","journal-title":"Nat. Biotechnol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"3606","DOI":"10.1002\/alz.13784","article-title":"The six brain-specific TAU isoforms and their role in Alzheimer\u2019s disease and related neurodegenerative dementia syndromes","volume":"20","author":"Buchholz","year":"2024","journal-title":"Alzheimer\u2019s Dement."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"431.e27","DOI":"10.1016\/j.neurobiolaging.2011.01.005","article-title":"Dynamic association of tau with neuronal membranes is regulated by phosphorylation","volume":"33","author":"Pooler","year":"2012","journal-title":"Neurobiol. Aging"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"18177","DOI":"10.1074\/jbc.M709715200","article-title":"Phosphorylation Regulates Tau Interactions with Src Homology 3 Domains of Phosphatidylinositol 3-Kinase, Phospholipase C\u03b31, Grb2, and Src Family Kinases","volume":"283","author":"Reynolds","year":"2008","journal-title":"J. Biol. Chem."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Miao, J., Shi, R., Li, L., Chen, F., Zhou, Y., Tung, Y.C., Hu, W., Gong, C.X., Iqbal, K., and Liu, F. (2019). Pathological Tau From Alzheimer\u2019s Brain Induces Site-Specific Hyperphosphorylation and SDS- and Reducing Agent-Resistant Aggregation of Tau in vivo. Front. Aging Neurosci., 11.","DOI":"10.3389\/fnagi.2019.00034"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"13812","DOI":"10.1074\/jbc.RA120.012587","article-title":"Truncation of Tau selectively facilitates its pathological activities","volume":"295","author":"Gu","year":"2020","journal-title":"J. Biol. Chem."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1038\/s41593-024-01801-5","article-title":"Tau filaments are tethered within brain extracellular vesicles in Alzheimer\u2019s disease","volume":"28","author":"Fowler","year":"2025","journal-title":"Nat. Neurosci."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"782","DOI":"10.1016\/j.ymthe.2021.09.020","article-title":"Extracellular vesicles: Major actors of heterogeneity in tau spreading among human tauopathies","volume":"30","author":"Leroux","year":"2022","journal-title":"Mol. Ther."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1093\/brain\/awaa376","article-title":"Alzheimer\u2019s disease brain-derived extracellular vesicles spread tau pathology in interneurons","volume":"144","author":"Ruan","year":"2021","journal-title":"Brain"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"107012","DOI":"10.1016\/j.nbd.2025.107012","article-title":"Interneuron transcriptomics reveals pathologic markers of Alzheimer\u2019s disease progression","volume":"213","author":"Chen","year":"2025","journal-title":"Neurobiol. Dis."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1016\/j.bbi.2021.01.010","article-title":"Early neuroinflammation is associated with lower amyloid and tau levels in cognitively normal older adults","volume":"94","author":"Albrecht","year":"2021","journal-title":"Brain Behav. Immun."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"e161987","DOI":"10.1172\/JCI161987","article-title":"Tau fibrils induce glial inflammation and neuropathology via TLR2 in Alzheimer\u2019s disease\u2013related mouse models","volume":"133","author":"Dutta","year":"2023","journal-title":"J. Clin. Investig."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1738","DOI":"10.1093\/brain\/awv081","article-title":"Reactive microglia drive tau pathology and contribute to the spreading of pathological tau in the brain","volume":"138","author":"Maphis","year":"2015","journal-title":"Brain"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1186\/s12974-018-1309-z","article-title":"The role of microglia in processing and spreading of bioactive tau seeds in Alzheimer\u2019s disease","volume":"15","author":"Hopp","year":"2018","journal-title":"J. Neuroinflammation"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.neuron.2010.08.023","article-title":"Regulation of tau pathology by the microglial fractalkine receptor","volume":"68","author":"Bhaskar","year":"2010","journal-title":"Neuron"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"466","DOI":"10.1186\/s12967-024-05256-x","article-title":"Microglia-derived exosomes selective sorted by YB-1 alleviate nerve damage and cognitive outcome in Alzheimer\u2019s disease","volume":"22","author":"Wei","year":"2024","journal-title":"J. Transl. Med."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1038\/s41419-020-2490-4","article-title":"Correction: Mesenchymal stem cell-derived exosomal miR-223 regulates neuronal cell apoptosis","volume":"11","author":"Wei","year":"2020","journal-title":"Cell Death Dis."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1002\/cbf.3184","article-title":"Downregulated serum miR-223 servers as biomarker in Alzheimer\u2019s disease","volume":"34","author":"Jia","year":"2016","journal-title":"Cell Biochem. Funct."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1416","DOI":"10.1021\/acschemneuro.8b00029","article-title":"A\u03b242 Protofibrils Interact with and Are Trafficked through Microglial-Derived Microvesicles","volume":"9","author":"Gouwens","year":"2018","journal-title":"ACS Chem. Neurosci."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"br15","DOI":"10.1091\/mbc.E24-04-0182","article-title":"RILP cleavage links an inflammatory state to enhanced tau propagation in a cell culture model of Alzheimer\u2019s disease","volume":"36","author":"King","year":"2025","journal-title":"Mol. Biol. Cell"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"109720","DOI":"10.1016\/j.celrep.2021.109720","article-title":"Proteopathic tau primes and activates interleukin-1\u03b2 via myeloid-cell-specific MyD88- and NLRP3-ASC-inflammasome pathway","volume":"36","author":"Jiang","year":"2021","journal-title":"Cell Rep."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1605","DOI":"10.1038\/s41374-021-00644-z","article-title":"Exosomal tau with seeding activity is released from Alzheimer\u2019s disease synapses, and seeding potential is associated with amyloid beta","volume":"101","author":"Miyoshi","year":"2021","journal-title":"Lab. Investig."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1186\/s13024-022-00562-8","article-title":"Trem2 deletion enhances tau dispersion and pathology through microglia exosomes","volume":"17","author":"Zhu","year":"2022","journal-title":"Mol. Neurodegener."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1186\/s13024-021-00440-9","article-title":"Plaque associated microglia hyper-secrete extracellular vesicles and accelerate tau propagation in a humanized APP mouse model","volume":"16","author":"Clayton","year":"2021","journal-title":"Mol. Neurodegener."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1059","DOI":"10.1002\/1873-3468.14336","article-title":"The Microglial membrane receptor TREM2 mediates exosome secretion to promote phagocytosis of amyloid-\u03b2 by microglia","volume":"596","author":"Huang","year":"2022","journal-title":"FEBS Lett."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1186\/s13024-020-00396-2","article-title":"P2RX7 inhibitor suppresses exosome secretion and disease phenotype in P301S tau transgenic mice","volume":"15","author":"Ruan","year":"2020","journal-title":"Mol. Neurodegener."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"150312","DOI":"10.1016\/j.bbrc.2024.150312","article-title":"Amyloid-\u03b2 oligomer-induced neurotoxicity by exosomal interactions between neuron and microglia","volume":"727","author":"Tong","year":"2024","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1221","DOI":"10.3233\/JAD-132450","article-title":"Bridging integrator 1 (BIN1) protein expression increases in the Alzheimer\u2019s disease brain and correlates with neurofibrillary tangle pathology","volume":"42","author":"Holler","year":"2014","journal-title":"J. Alzheimers Dis."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"9477","DOI":"10.1038\/s41598-019-45676-0","article-title":"BIN1 favors the spreading of Tau via extracellular vesicles","volume":"9","author":"Crotti","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1561","DOI":"10.1093\/brain\/awac318","article-title":"Loss of forebrain BIN1 attenuates hippocampal pathology and neuroinflammation in a tauopathy model","volume":"146","author":"Ponnusamy","year":"2023","journal-title":"Brain"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"21170","DOI":"10.1038\/s41598-022-25131-3","article-title":"The effects of microglia on tauopathy progression can be quantified using Nexopathy in silico (Nexis) models","volume":"12","author":"Anand","year":"2022","journal-title":"Sci. Rep."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1186\/s40478-020-00931-8","article-title":"Association of A\u03b2 with ceramide-enriched astrosomes mediates A\u03b2 neurotoxicity","volume":"8","author":"Elsherbini","year":"2020","journal-title":"Acta Neuropathol. Commun."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"e2200944119","DOI":"10.1073\/pnas.2200944119","article-title":"Mapping secretome-mediated interaction between paired neuron-macrophage single cells","volume":"119","author":"Deng","year":"2022","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"8812","DOI":"10.1523\/JNEUROSCI.1318-23.2023","article-title":"Nascent A\u03b242 Fibrillization in Synaptic Endosomes Precedes Plaque Formation in a Mouse Model of Alzheimer\u2019s-like \u03b2-Amyloidosis","volume":"43","author":"Eckman","year":"2023","journal-title":"J. Neurosci."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"e2304025","DOI":"10.1002\/advs.202304025","article-title":"Exosomes Derived from M2 Microglial Cells Modulated by 1070-nm Light Improve Cognition in an Alzheimer\u2019s Disease Mouse Model","volume":"10","author":"Chen","year":"2023","journal-title":"Adv. Sci."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"2401","DOI":"10.2147\/DDDT.S417465","article-title":"An Exosome-Based Therapeutic Strategy Targeting Neuroinflammation in Alzheimer\u2019s Disease with Berberine and Palmatine","volume":"17","author":"Zhao","year":"2023","journal-title":"Drug Des. Dev. Ther."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1186\/s13024-016-0143-y","article-title":"The release and trans-synaptic transmission of Tau via exosomes","volume":"12","author":"Wang","year":"2017","journal-title":"Mol. Neurodegener."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"e21965","DOI":"10.1002\/syn.21965","article-title":"Spread of tau down neural circuits precedes synapse and neuronal loss in the rTgTauEC mouse model of early Alzheimer\u2019s disease","volume":"71","author":"Pickett","year":"2017","journal-title":"Synapse"},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Jahangard, Y., Monfared, H., Moradi, A., Zare, M., Mirnajafi-Zadeh, J., and Mowla, S.J. (2020). Therapeutic Effects of Transplanted Exosomes Containing miR-29b to a Rat Model of Alzheimer\u2019s Disease. Front. Neurosci., 14.","DOI":"10.3389\/fnins.2020.00564"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"101694","DOI":"10.1016\/j.pneurobio.2019.101694","article-title":"Exosomal miRNAs in central nervous system diseases: Biomarkers, pathological mediators, protective factors and therapeutic agents","volume":"183","author":"Xia","year":"2019","journal-title":"Prog. Neurobiol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"7027380","DOI":"10.1155\/2017\/7027380","article-title":"Potential Roles of Exosomal MicroRNAs as Diagnostic Biomarkers and Therapeutic Application in Alzheimer\u2019s Disease","volume":"2017","author":"Chen","year":"2017","journal-title":"Neural Plast."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1186\/1479-5876-12-162","article-title":"Exosomal miRNAs as potential biomarkers of cardiovascular risk in children","volume":"12","author":"Khalyfa","year":"2014","journal-title":"J. Transl. Med."},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Visconte, C., Fenoglio, C., Serpente, M., Muti, P., Sacconi, A., Rigoni, M., Arighi, A., Borracci, V., Arcaro, M., and Arosio, B. (2023). Altered Extracellular Vesicle miRNA Profile in Prodromal Alzheimer\u2019s Disease. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms241914749"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"114061","DOI":"10.1016\/j.celrep.2024.114061","article-title":"Human brain small extracellular vesicles contain selectively packaged, full-length mRNA","volume":"43","author":"Ransom","year":"2024","journal-title":"Cell Rep."},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Garcia, G., Pinto, S., Ferreira, S., Lopes, D., Serrador, M.J., Fernandes, A., Vaz, A.R., Mendon\u00e7a, A., Edenhofer, F., and Malm, T. (2022). Emerging Role of miR-21-5p in Neuron-Glia Dysregulation and Exosome Transfer Using Multiple Models of Alzheimer\u2019s Disease. Cells, 11.","DOI":"10.3390\/cells11213377"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"133","DOI":"10.20517\/evcna.2023.13","article-title":"Synaptic proteins in neuron-derived extracellular vesicles as biomarkers for Alzheimer\u2019s disease: Novel methodology and clinical proof of concept","volume":"4","author":"Eitan","year":"2023","journal-title":"Extracell. Vesicles Circ. Nucl. Acids"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1186\/s12951-023-01793-7","article-title":"Plasma extracellular vesicles reveal early molecular differences in amyloid positive patients with early-onset mild cognitive impairment","volume":"21","author":"Cano","year":"2023","journal-title":"J. Nanobiotechnol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1007\/s12195-016-0458-3","article-title":"Elucidation of Exosome Migration across the Blood-Brain Barrier Model In Vitro","volume":"9","author":"Chen","year":"2016","journal-title":"Cell Mol. Bioeng."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"8826","DOI":"10.1007\/s12035-018-1032-x","article-title":"MicroRNA Expression Levels Are Altered in the Cerebrospinal Fluid of Patients with Young-Onset Alzheimer\u2019s Disease","volume":"55","author":"McKeever","year":"2018","journal-title":"Mol. Neurobiol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"e12432","DOI":"10.1002\/jev2.12432","article-title":"Surface protein profiling and subtyping of extracellular vesicles in body fluids reveals non-CSF biomarkers of Alzheimer\u2019s disease","volume":"13","author":"Cai","year":"2024","journal-title":"J. Extracell. Vesicles"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1159\/000505851","article-title":"A Pilot Study of Urinary Exosomes in Alzheimer\u2019s Disease","volume":"19","author":"Sun","year":"2019","journal-title":"Neurodegener. Dis."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"111046","DOI":"10.1016\/j.brainresbull.2024.111046","article-title":"Induction of tau pathology and motor dysfunction in mice by urinary exosomes from progressive supranuclear palsy patients","volume":"216","author":"Li","year":"2024","journal-title":"Brain Res. Bull."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1186\/s13195-022-01133-1","article-title":"Proteomic profiling of circulating plasma exosomes reveals novel biomarkers of Alzheimer\u2019s disease","volume":"14","author":"Cai","year":"2022","journal-title":"Alzheimer\u2019s Res. Ther."},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Longobardi, A., Benussi, L., Nicsanu, R., Bellini, S., Ferrari, C., Saraceno, C., Zanardini, R., Catania, M., Di Fede, G., and Squitti, R. (2021). Plasma Extracellular Vesicle Size and Concentration Are Altered in Alzheimer\u2019s Disease, Dementia With Lewy Bodies, and Frontotemporal Dementia. Front. Cell Dev. Biol., 9.","DOI":"10.3389\/fcell.2021.667369"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1071","DOI":"10.1016\/j.jalz.2019.05.002","article-title":"Concordance between the assessment of A\u03b242, T-tau, and P-T181-tau in peripheral blood neuronal-derived exosomes and cerebrospinal fluid","volume":"15","author":"Jia","year":"2019","journal-title":"Alzheimers Dement."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"600","DOI":"10.1016\/j.jalz.2014.06.008","article-title":"Identification of preclinical Alzheimer\u2019s disease by a profile of pathogenic proteins in neurally derived blood exosomes: A case-control study","volume":"11","author":"Fiandaca","year":"2015","journal-title":"Alzheimers Dement."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1093","DOI":"10.1111\/cns.13846","article-title":"Amyloid-\u03b2 protein and MicroRNA-384 in NCAM-Labeled exosomes from peripheral blood are potential diagnostic markers for Alzheimer\u2019s disease","volume":"28","author":"Li","year":"2022","journal-title":"CNS Neurosci. Ther."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1771","DOI":"10.1038\/s41591-024-02937-4","article-title":"Plasma extracellular vesicle tau and TDP-43 as diagnostic biomarkers in FTD and ALS","volume":"30","author":"Chatterjee","year":"2024","journal-title":"Nat. Med."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1340","DOI":"10.1001\/jamaneurol.2019.2462","article-title":"Association of Extracellular Vesicle Biomarkers With Alzheimer Disease in the Baltimore Longitudinal Study of Aging","volume":"76","author":"Kapogiannis","year":"2019","journal-title":"JAMA Neurol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1002\/alz.12166","article-title":"Blood neuro-exosomal synaptic proteins predict Alzheimer\u2019s disease at the asymptomatic stage","volume":"17","author":"Jia","year":"2021","journal-title":"Alzheimers Dement."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"eabm3088","DOI":"10.1126\/sciadv.abm3088","article-title":"Sensitive detection of multiple blood biomarkers via immunomagnetic exosomal PCR for the diagnosis of Alzheimer\u2019s disease","volume":"10","author":"Hu","year":"2024","journal-title":"Sci. Adv."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1186\/s13195-024-01508-6","article-title":"Comparison of plasma soluble and extracellular vesicles-associated biomarkers in Alzheimer\u2019s disease patients and cognitively normal individuals","volume":"16","author":"Boyer","year":"2024","journal-title":"Alzheimers Res. Ther."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"105279","DOI":"10.1016\/j.jprot.2024.105279","article-title":"Proteomics of plasma-derived extracellular vesicles reveals S100A8 as a novel biomarker for Alzheimer\u2019s disease: A preliminary study","volume":"308","author":"Zhang","year":"2024","journal-title":"J. Proteom."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1038\/s41398-020-0801-2","article-title":"Neurogranin as a cognitive biomarker in cerebrospinal fluid and blood exosomes for Alzheimer\u2019s disease and mild cognitive impairment","volume":"10","author":"Liu","year":"2020","journal-title":"Transl. Psychiatry"},{"key":"ref_81","doi-asserted-by":"crossref","unstructured":"S\u00e1nchez-Melgar, A., Albasanz, J.L., Gri\u00f1\u00e1n-Ferr\u00e9, C., Pall\u00e0s, M., and Mart\u00edn, M. (2020). Adenosine and Metabotropic Glutamate Receptors Are Present in Blood Serum and Exosomes from SAMP8 Mice: Modulation by Aging and Resveratrol. Cells, 9.","DOI":"10.3390\/cells9071628"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"105947","DOI":"10.1016\/j.nbd.2022.105947","article-title":"Oligomeric \u03b1-synuclein and tau aggregates in NDEVs differentiate Parkinson\u2019s disease from atypical parkinsonisms","volume":"176","author":"Meloni","year":"2023","journal-title":"Neurobiol. Dis."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"2663","DOI":"10.1002\/mds.28591","article-title":"Validation of \u03b1-Synuclein in L1CAM-Immunocaptured Exosomes as a Biomarker for the Stratification of Parkinsonian Syndromes","volume":"36","author":"Jiang","year":"2021","journal-title":"Mov. Disord."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"869","DOI":"10.3233\/JAD-230347","article-title":"Circulating Exosomes from Alzheimer\u2019s Disease Suppress Vascular Endothelial-Cadherin Expression and Induce Barrier Dysfunction in Recipient Brain Microvascular Endothelial Cell","volume":"95","author":"Bei","year":"2023","journal-title":"J. Alzheimers Dis."},{"key":"ref_85","doi-asserted-by":"crossref","unstructured":"Krokidis, M.G., Pucha, K.A., Mustapic, M., Exarchos, T.P., Vlamos, P., and Kapogiannis, D. (2024). Lipidomic Analysis of Plasma Extracellular Vesicles Derived from Alzheimer\u2019s Disease Patients. Cells, 13.","DOI":"10.3390\/cells13080702"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"4141","DOI":"10.1096\/fj.201600816R","article-title":"Decreased synaptic proteins in neuronal exosomes of frontotemporal dementia and Alzheimer\u2019s disease","volume":"30","author":"Goetzl","year":"2016","journal-title":"FASEB J."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1186\/s13195-023-01334-2","article-title":"PACAP-Sirtuin3 alleviates cognitive impairment through autophagy in Alzheimer\u2019s disease","volume":"15","author":"Wang","year":"2023","journal-title":"Alzheimers Res. Ther."},{"key":"ref_88","doi-asserted-by":"crossref","unstructured":"Eren, E., Leoutsakos, J.M., Troncoso, J., Lyketsos, C.G., Oh, E.S., and Kapogiannis, D. (2022). Neuronal-Derived EV Biomarkers Track Cognitive Decline in Alzheimer\u2019s Disease. Cells, 11.","DOI":"10.3390\/cells11030436"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"627","DOI":"10.1093\/brain\/awad361","article-title":"Extracellular vesicle proteome unveils cathepsin B connection to Alzheimer\u2019s disease pathogenesis","volume":"147","author":"Yuyama","year":"2024","journal-title":"Brain"},{"key":"ref_90","doi-asserted-by":"crossref","unstructured":"Muraoka, S., Jedrychowski, M.P., Yanamandra, K., Ikezu, S., Gygi, S.P., and Ikezu, T. (2020). Proteomic Profiling of Extracellular Vesicles Derived from Cerebrospinal Fluid of Alzheimer\u2019s Disease Patients: A Pilot Study. Cells, 9.","DOI":"10.3390\/cells9091959"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"e70050","DOI":"10.1002\/alz.70050","article-title":"Preclinical Alzheimer\u2019s disease shows alterations in circulating neuronal-derived extracellular vesicle microRNAs in a multiethnic cohort","volume":"21","author":"Reho","year":"2025","journal-title":"Alzheimers Dement."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"1458","DOI":"10.55730\/1300-0144.5484","article-title":"Determination of miR-373 and miR-204 levels in neuronal exosomes in Alzheimer\u2019s disease","volume":"52","author":"Tezcan","year":"2022","journal-title":"Turk. J. Med. Sci."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"112063","DOI":"10.1016\/j.mad.2025.112063","article-title":"miR-132-3p is down-regulated in plasma and CD171+ extracellular vesicles isolated from patients with mild Alzheimer\u2019s disease","volume":"225","author":"Sbriscia","year":"2025","journal-title":"Mech. Ageing Dev."},{"key":"ref_94","doi-asserted-by":"crossref","unstructured":"Subasinghe, K., Hall, C., Rowe, M., Zhou, Z., Barber, R., and Phillips, N. (2025). Neuronal Enriched Extracellular Vesicle miR-122-5p as a Potential Biomarker for Alzheimer\u2019s Disease. Cells, 14.","DOI":"10.3390\/cells14221784"},{"key":"ref_95","doi-asserted-by":"crossref","unstructured":"Mosquera-Heredia, M.I., Vidal, O.M., Morales, L.C., Silvera-Redondo, C., Barcel\u00f3, E., Allegri, R., Arcos-Burgos, M., V\u00e9lez, J.I., and Garavito-Galofre, P. (2024). Long Non-Coding RNAs and Alzheimer\u2019s Disease: Towards Personalized Diagnosis. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25147641"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12974-022-02393-2","article-title":"Exosomes derived from bone-marrow mesenchymal stem cells alleviate cognitive decline in AD-like mice by improving BDNF-related neuropathology","volume":"19","author":"Liu","year":"2022","journal-title":"J. Neuroinflammation"},{"key":"ref_97","doi-asserted-by":"crossref","unstructured":"Zhao, Y., Gu, Y., Zhang, Q., Liu, H., and Liu, Y. (2023). The Potential Roles of Exosomes Carrying APP and Tau Cleavage Products in Alzheimer\u2019s Disease. J. Clin. Med., 12.","DOI":"10.3390\/jcm12051883"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"6891","DOI":"10.1111\/febs.16055","article-title":"Exosomal and vesicle-free tau seeds-propagation and convergence in endolysosomal permeabilization","volume":"289","author":"Polanco","year":"2022","journal-title":"FEBS J."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"1324730","DOI":"10.1080\/20013078.2017.1324730","article-title":"Comprehensive toxicity and immunogenicity studies reveal minimal effects in mice following sustained dosing of extracellular vesicles derived from HEK293T cells","volume":"6","author":"Zhu","year":"2017","journal-title":"J. Extracell. Vesicles"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"1836","DOI":"10.1038\/mt.2016.126","article-title":"Exosome-mediated Delivery of Hydrophobically Modified siRNA for Huntingtin mRNA Silencing","volume":"24","author":"Didiot","year":"2016","journal-title":"Mol. Ther."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"2980","DOI":"10.1038\/ncomms3980","article-title":"Sumoylated hnRNPA2B1 controls the sorting of miRNAs into exosomes through binding to specific motifs","volume":"4","author":"Mittelbrunn","year":"2013","journal-title":"Nat. Commun."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"e101143","DOI":"10.1136\/gpsych-2023-101143","article-title":"Clinical safety and efficacy of allogenic human adipose mesenchymal stromal cells-derived exosomes in patients with mild to moderate Alzheimer\u2019s disease: A phase I\/II clinical trial","volume":"36","author":"Xie","year":"2023","journal-title":"Gen. Psychiatr."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"1777","DOI":"10.1021\/bc500291r","article-title":"Surface functionalization of exosomes using click chemistry","volume":"25","author":"Smyth","year":"2014","journal-title":"Bioconjug. Chem."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"119675","DOI":"10.1016\/j.biomaterials.2019.119675","article-title":"Post-production modifications of murine mesenchymal stem cell (mMSC) derived extracellular vesicles (EVs) and impact on their cellular interaction","volume":"231","author":"Aarrass","year":"2020","journal-title":"Biomaterials"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1186\/s12951-022-01462-1","article-title":"Engineering a HEK-293T exosome-based delivery platform for efficient tumor-targeting chemotherapy\/internal irradiation combination therapy","volume":"20","author":"Wang","year":"2022","journal-title":"J. Nanobiotechnology"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1186\/s12951-025-03426-7","article-title":"Efficient delivery of small RNAs to podocytes in vitro by direct exosome transfection","volume":"23","author":"Lange","year":"2025","journal-title":"J. Nanobiotechnology"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"1335","DOI":"10.1007\/s11011-024-01395-8","article-title":"Exosomal MicroRNAs modulate the cognitive function in fasudil treated APPswe\/PSEN1dE9 transgenic (APP\/PS1) mice model of Alzheimer\u2019s disease","volume":"39","author":"Yan","year":"2024","journal-title":"Metab. Brain Dis."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"4351","DOI":"10.7150\/thno.52436","article-title":"Ultrasound-mediated augmented exosome release from astrocytes alleviates amyloid-\u03b2-induced neurotoxicity","volume":"11","author":"Deng","year":"2021","journal-title":"Theranostics"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"e13748","DOI":"10.1111\/acel.13748","article-title":"Exosomal miR-532-5p induced by long-term exercise rescues blood-brain barrier function in 5XFAD mice via downregulation of EPHA4","volume":"22","author":"Liang","year":"2023","journal-title":"Aging Cell"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"10770","DOI":"10.1007\/s12035-024-04251-z","article-title":"Combined Catalpol and Tetramethylpyrazine Promote Axonal Plasticity in Alzheimer\u2019s Disease by Inducing Astrocytes to Secrete Exosomes Carrying CDK5 mRNA and Regulating STAT3 Phosphorylation","volume":"61","author":"Chen","year":"2024","journal-title":"Mol. Neurobiol."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"1068","DOI":"10.1002\/sctm.19-0327","article-title":"Intranasal delivery of mesenchymal stem cell-derived extracellular vesicles exerts immunomodulatory and neuroprotective effects in a 3xTg model of Alzheimer\u2019s disease","volume":"9","author":"Losurdo","year":"2020","journal-title":"Stem Cells Transl. Med."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"1626","DOI":"10.4103\/1673-5374.255978","article-title":"Mesenchymal stem cell-derived exosomes promote neurogenesis and cognitive function recovery in a mouse model of Alzheimer\u2019s disease","volume":"14","year":"2019","journal-title":"Neural Regen. Res."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"15731","DOI":"10.1038\/s41598-023-42485-4","article-title":"Stem cells-derived exosomes alleviate neurodegeneration and Alzheimer\u2019s pathogenesis by ameliorating neuroinflamation, and regulating the associated molecular pathways","volume":"13","author":"Khan","year":"2023","journal-title":"Sci. Rep."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"488","DOI":"10.1002\/ana.27001","article-title":"Human-Derived Induced GABAergic Progenitor Cells Improve Cognitive Function in Mice and Inhibit Astrocyte Activation with Anti-Inflammatory Exosomes","volume":"96","author":"Chen","year":"2024","journal-title":"Ann. Neurol."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1007\/s11011-024-01503-8","article-title":"Molecular intersections of traumatic brain injury and Alzheimer\u2019s disease: The role of ADMSC-derived exosomes and hub genes in microglial polarization","volume":"40","author":"Li","year":"2024","journal-title":"Metab. Brain Dis."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"7513","DOI":"10.1111\/jcmm.16787","article-title":"ADMSC Exo-MicroRNA-22 improve neurological function and neuroinflammation in mice with Alzheimer\u2019s disease","volume":"25","author":"Zhai","year":"2021","journal-title":"J. Cell Mol. Med."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"8129","DOI":"10.7150\/thno.62069","article-title":"Mesenchymal stem cell-derived extracellular vesicles ameliorate Alzheimer\u2019s disease-like phenotypes in a preclinical mouse model","volume":"11","author":"Cone","year":"2021","journal-title":"Theranostics"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1186\/s12929-024-01072-z","article-title":"Neuroprotective effects of intranasal extracellular vesicles from human platelet concentrates supernatants in traumatic brain injury and Parkinson\u2019s disease models","volume":"31","author":"Delila","year":"2024","journal-title":"J. Biomed. Sci."},{"key":"ref_119","doi-asserted-by":"crossref","unstructured":"Smith, J., Field, M., and Sugaya, K. (2025). Brain-Homing Peptide Expression on the Membrane Enhances the Delivery of Exosomes to Neural Cells and Tissue. Neuroglia, 6.","DOI":"10.3390\/neuroglia6010003"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"eadi4830","DOI":"10.1126\/scitranslmed.adi4830","article-title":"Engineered exosomes with a photoinducible protein delivery system enable CRISPR-Cas-based epigenome editing in Alzheimer\u2019s disease","volume":"16","author":"Han","year":"2024","journal-title":"Sci. Transl. Med."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"101738","DOI":"10.1016\/j.mtbio.2025.101738","article-title":"Engineered exosomes improve the effects of curcumin on protecting mitochondria of neurons in Alzheimer\u2019s disease","volume":"32","author":"Ding","year":"2025","journal-title":"Mater. Today Bio"},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"11753","DOI":"10.1021\/acsnano.3c13150","article-title":"Biomimetic Nanovesicles as a Dual Gene Delivery System for the Synergistic Gene Therapy of Alzheimer\u2019s Disease","volume":"18","author":"Jiang","year":"2024","journal-title":"ACS Nano"},{"key":"ref_123","unstructured":"(2026, February 08). A Multi-Center, Open, Single-Arm, Basket-Design Clinical Trial to Evaluate the Safety and Efficacy of Human Umbilical Cord Mesenchymal Stem Cell-Derived Small Extracellular Vesicles hUC-MSC-sEV-001 Nasal Drops for the Treatment of Multiple Neurodegenerative Diseases, Available online: https:\/\/clinicaltrials.gov\/study\/NCT06607900."},{"key":"ref_124","unstructured":"(2026, February 08). Safety of Cultured Allogeneic Adult Umbilical Cord Derived Mesenchymal Stem Cell Exosome Intranasal Instillation for the Treatment of Parkinson\u2019s Disease, Available online: https:\/\/clinicaltrials.gov\/study\/NCT05152394."},{"key":"ref_125","unstructured":"(2026, February 08). An Exploratory Study on the Use of Intranasal Administration of Small Extracellular Vesicles for the Treatment of Amyotrophic Lateral Sclerosis, L.Shengqi Medical Technology Co and L. Viyun Biomedical Research Institute Co., Editor, Available online: https:\/\/clinicaltrials.gov\/study\/NCT06598202."},{"key":"ref_126","unstructured":"(2026, February 08). Patients With ALS and Other Motor Discorders Will be Treated With Mesenchymal Cell Exosome Solution, Available online: https:\/\/clinicaltrials.gov\/study\/NCT07105371."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"1700611","DOI":"10.1002\/advs.201700611","article-title":"Exosome-Liposome Hybrid Nanoparticles Deliver CRISPR\/Cas9 System in MSCs","volume":"5","author":"Lin","year":"2018","journal-title":"Adv. Sci."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"11585","DOI":"10.1038\/s41598-021-91129-y","article-title":"Potential and challenges of specifically isolating extracellular vesicles from heterogeneous populations","volume":"11","author":"Allelein","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"3599","DOI":"10.1021\/acs.jproteome.8b00479","article-title":"Comparison of an Optimized Ultracentrifugation Method versus Size-Exclusion Chromatography for Isolation of Exosomes from Human Serum","volume":"17","author":"An","year":"2018","journal-title":"J. Proteome Res."},{"key":"ref_130","unstructured":"Posch, A. (2015). A Protocol for Exosome Isolation and Characterization: Evaluation of Ultracentrifugation, Density-Gradient Separation, and Immunoaffinity Capture Methods. Proteomic Profiling: Methods and Protocols, Springer."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"e00241","DOI":"10.1016\/j.plabm.2021.e00241","article-title":"Coupling size exclusion chromatography to ultracentrifugation improves detection of exosomal proteins from human plasma by LC-MS","volume":"26","author":"Alameldin","year":"2021","journal-title":"Pract. Lab. Med."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"7923","DOI":"10.2147\/IJN.S444582","article-title":"Engineered Exosome for Drug Delivery: Recent Development and Clinical Applications","volume":"18","author":"Tian","year":"2023","journal-title":"Int. J. Nanomed."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"3533","DOI":"10.1021\/acsabm.5c00318","article-title":"Rapid Isolation and Characterization of Exosomes through a Single-Step, Label-Free Protein Biomarker Analysis","volume":"8","author":"Ambrosius","year":"2025","journal-title":"ACS Appl. Bio Mater."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"25419","DOI":"10.1038\/s41598-024-75406-0","article-title":"Phosphorylated tau in cerebrospinal fluid-derived extracellular vesicles in Alzheimer\u2019s disease: A pilot study","volume":"14","author":"Sattarov","year":"2024","journal-title":"Sci. Rep."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1007\/s11481-019-09884-9","article-title":"Macrophage-Derived Extracellular Vesicles as Drug Delivery Systems for Triple Negative Breast Cancer (TNBC) Therapy","volume":"15","author":"Haney","year":"2020","journal-title":"J. Neuroimmune Pharmacol."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"103628","DOI":"10.1016\/j.critrevonc.2022.103628","article-title":"New advances in exosome-based targeted drug delivery systems","volume":"172","author":"Ferreira","year":"2022","journal-title":"Crit. Rev. Oncol. Hematol."},{"key":"ref_137","doi-asserted-by":"crossref","unstructured":"Sayeed, N., and Sugaya, K. (2022). Exosome mediated Tom40 delivery protects against hydrogen peroxide-induced oxidative stress by regulating mitochondrial function. PLoS ONE, 17.","DOI":"10.1371\/journal.pone.0272511"},{"key":"ref_138","doi-asserted-by":"crossref","unstructured":"Vaidya, M., Kimura, A., Bajaj, A., and Sugaya, K. (2024). 3\u2032-UTR Sequence of Exosomal NANOGP8 DNA as an Extracellular Vesicle-Localization Signal. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25137294"},{"key":"ref_139","doi-asserted-by":"crossref","unstructured":"Vaidya, M., Bacchus, M., and Sugaya, K. (2018). Differential sequences of exosomal NANOG DNA as a potential diagnostic cancer marker. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0197782"},{"key":"ref_140","doi-asserted-by":"crossref","unstructured":"Ben, X.-Y., Wang, Y.-R., Zheng, H.-H., Li, D.-X., Ren, R., Ni, P.-L., Zhang, H.-Y., Feng, R.-J., Li, Y.-Q., and Li, Q.-F. (2022). Construction of Exosomes that Overexpress CD47 and Evaluation of Their Immune Escape. Front. Bioeng. Biotechnol., 10.","DOI":"10.3389\/fbioe.2022.936951"},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1016\/j.omtn.2022.06.011","article-title":"Delivery of therapeutic small interfering RNA: The current patent-based landscape","volume":"29","author":"Chen","year":"2022","journal-title":"Mol. Ther. Nucleic Acids"},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"1623","DOI":"10.1080\/17425247.2023.2292678","article-title":"Advancements in pH-responsive nanocarriers: Enhancing drug delivery for tumor therapy","volume":"20","author":"Chen","year":"2023","journal-title":"Expert. Opin. Drug Deliv."},{"key":"ref_143","doi-asserted-by":"crossref","unstructured":"Shi, X., He, W., Xu, H., Clark, L., Zeng, H.M., Gupta, A., Mirle, N., Fenno, L., and Wang, H. (2025). Ultrasound-activated drug release with extracellular vesicles. bioRxiv.","DOI":"10.1101\/2025.08.11.669710"},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"011503","DOI":"10.1063\/1.5087122","article-title":"Challenges and opportunities in exosome research\u2014Perspectives from biology, engineering, and cancer therapy","volume":"3","author":"Li","year":"2019","journal-title":"APL Bioeng."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1186\/s12943-022-01515-x","article-title":"Engineered exosomes as an in situ DC-primed vaccine to boost antitumor immunity in breast cancer","volume":"21","author":"Huang","year":"2022","journal-title":"Mol. Cancer"},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"716","DOI":"10.1016\/j.devcel.2017.11.018","article-title":"Atg5 Disassociates the V1V0-ATPase to Promote Exosome Production and Tumor Metastasis Independent of Canonical Macroautophagy","volume":"43","author":"Guo","year":"2017","journal-title":"Dev. Cell"},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1186\/s12974-024-03019-5","article-title":"Microglia-derived exosomes modulate myelin regeneration via miR-615-5p\/MYRF axis","volume":"21","author":"Ji","year":"2024","journal-title":"J. Neuroinflammation"},{"key":"ref_148","doi-asserted-by":"crossref","unstructured":"Ghosh, M., and Pearse, D.D. (2024). The Yin and Yang of Microglia-Derived Extracellular Vesicles in CNS Injury and Diseases. 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