{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T11:05:31Z","timestamp":1785236731848,"version":"3.55.0"},"reference-count":184,"publisher":"OAE Publishing Inc.","issue":"3","content-domain":{"domain":["oaepublish.com"],"crossmark-restriction":false},"short-container-title":["Extracell Vesicles Circ Nucleic Acids."],"abstract":"<jats:p>Alzheimer\u2019s disease (AD), a progressive neurodegenerative disorder, remains a major global health challenge owing to its complex pathogenesis and the presence of the blood-brain barrier (BBB), which substantially limits the delivery of effective therapeutics to the brain. Extracellular vesicles (EVs), which exhibit favorable biocompatibility, low immunogenicity, and an intrinsic capacity to cross the BBB, have emerged as promising therapeutic agents and delivery platforms for AD. This review focuses on the therapeutic potential of EV-based interventions in AD and summarizes recent advances in EV-mediated modulation of AD-related pathological processes, including amyloid-\u03b2 (A\u03b2) clearance, tau protein regulation, neuroinflammation suppression, oxidative stress attenuation, and synaptic repair. Although EV-based therapies offer notable advantages, such as targeted BBB penetration and reduced immunogenic responses, their clinical translation remains constrained by safety concerns, including off-target effects, dose-dependent toxicity, and potential disturbances in neuroplasticity. In addition, this review discusses EV engineering strategies aimed at regulating the gut-brain axis (GBA), enhancing brain targeting, and advancing clinical translation. EV-based therapeutic interventions should therefore be developed within a safety-oriented framework supported by rigorous short- and long-term toxicological evaluation. Overall, this review highlights the therapeutic promise of EVs for AD while underscoring the need for rational engineering, standardized characterization, and safety-centered translational strategies to ensure clinical feasibility.<\/jats:p>","DOI":"10.20517\/evcna.2026.43","type":"journal-article","created":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T10:37:32Z","timestamp":1785235052000},"page":"1158-88","update-policy":"https:\/\/doi.org\/10.20517\/oae.crossmark.policy","source":"Crossref","is-referenced-by-count":0,"title":["Extracellular vesicles for Alzheimer\u2019s disease therapy: mechanisms, engineering strategies, and clinical translation"],"prefix":"10.20517","volume":"7","author":[{"given":"Ailin","family":"Wu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Zeng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yilin","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Legao","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shunyuan","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianwei","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaozhou","family":"Mou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoru","family":"Chang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"8410","published-online":{"date-parts":[[2026,7,28]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/s0140-6736(25)01294-2"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.24976\/discov.med.202436189.179"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1007\/7854_2024_527"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1002\/alz.13809"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2025.177520"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1007\/s11011-024-01507-4"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1186\/s40001-025-02886-9"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1177\/13872877241283677"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurot.2025.e00540"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1038\/s41587-024-02487-7"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-025-03443-1"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.7150\/thno.81860"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.260201"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-025-05216-6"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1002\/jev2.12416"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1002\/jev2.12404"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-023-01436-1"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.14336\/ad.2023.1206"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1016\/j.arr.2023.102088"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1002\/adma.202419768"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1016\/j.gendis.2025.101846"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.3390\/jcm15062357"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-025-02103-0"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2024.1391517"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1016\/j.apsb.2024.10.004"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1002\/alz.70390"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-026-71831-z"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-025-66157-1"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awab372"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1016\/j.chembiol.2026.03.017"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1002\/ibra.12155"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-025-03528-x"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1007\/s12264-025-01572-4"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1096\/fj.201801319r"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.ade0293"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1002\/alz.71148"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1016\/j.bnd.2024.12.006"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.7150\/thno.103596"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-022-02393-2"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2020.09.019"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-025-02453-y"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2024.106700"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.7150\/thno.62069"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1186\/s13195-021-00791-x"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-022-03055-3"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.4103\/1673-5374.385839"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2022.874102"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-023-03733-w"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1038\/s12276-023-01084-z"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.3390\/nu17233771"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1016\/bs.acc.2025.01.005"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2024.149165"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1038\/nn.4132"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1186\/s13024-022-00581-5"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.1002\/glia.24485"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-024-01801-5"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.1186\/s13024-022-00562-8"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.1016\/j.mad.2021.111438"},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.1038\/s41380-025-02976-4"},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2025.07.024"},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.1016\/j.ahr.2025.100267"},{"key":"B62","doi-asserted-by":"publisher","DOI":"10.3390\/cells8121605"},{"key":"B63","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2025.1592578"},{"key":"B64","doi-asserted-by":"publisher","DOI":"10.4103\/NRR.NRR-D-25-00404"},{"key":"B65","doi-asserted-by":"publisher","DOI":"10.1002\/sctm.19-0327"},{"key":"B66","doi-asserted-by":"publisher","DOI":"10.1111\/cns.70634"},{"key":"B67","doi-asserted-by":"publisher","DOI":"10.1002\/alz.12683"},{"key":"B68","doi-asserted-by":"publisher","DOI":"10.1016\/j.arr.2025.102713"},{"key":"B69","doi-asserted-by":"publisher","DOI":"10.1016\/j.fshw.2022.10.009"},{"key":"B70","doi-asserted-by":"publisher","DOI":"10.1002\/smll.202401045"},{"key":"B71","doi-asserted-by":"publisher","DOI":"10.1007\/s12031-022-01996-x"},{"key":"B72","doi-asserted-by":"publisher","DOI":"10.3390\/antiox10071088"},{"key":"B73","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2025.115143"},{"key":"B74","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1703920114"},{"key":"B75","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2025.123403"},{"key":"B76","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-023-06120-6"},{"key":"B77","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-024-01911-3"},{"key":"B78","doi-asserted-by":"publisher","DOI":"10.1007\/s11033-023-09021-z"},{"key":"B79","doi-asserted-by":"publisher","DOI":"10.1002\/alz.13490"},{"key":"B80","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-024-01763-8"},{"key":"B81","doi-asserted-by":"publisher","DOI":"10.1016\/j.arr.2026.103168"},{"key":"B82","doi-asserted-by":"publisher","DOI":"10.1002\/ame2.70104"},{"key":"B83","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-05858-2"},{"key":"B84","doi-asserted-by":"publisher","DOI":"10.1016\/j.nantod.2025.102932"},{"key":"B85","doi-asserted-by":"publisher","DOI":"10.1186\/s13024-019-0322-8"},{"key":"B86","doi-asserted-by":"publisher","DOI":"10.1038\/s41583-023-00711-y"},{"key":"B87","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-025-01973-8"},{"key":"B88","doi-asserted-by":"publisher","DOI":"10.1016\/j.actbio.2023.12.009"},{"key":"B89","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-024-01730-3"},{"key":"B90","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.3002727"},{"key":"B91","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202105586"},{"key":"B92","doi-asserted-by":"publisher","DOI":"10.1111\/cns.14661"},{"key":"B93","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-024-03019-5"},{"key":"B94","doi-asserted-by":"publisher","DOI":"10.3233\/jad-240299"},{"key":"B95","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.102.041616"},{"key":"B96","doi-asserted-by":"publisher","DOI":"10.4140\/tcp.n.2004.827"},{"key":"B97","doi-asserted-by":"publisher","DOI":"10.1159\/000338236"},{"key":"B98","doi-asserted-by":"publisher","DOI":"10.3233\/jad-170848"},{"key":"B99","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2025.177695"},{"key":"B100","doi-asserted-by":"publisher","DOI":"10.2147\/ijn.s513816"},{"key":"B101","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexcr.2021.112635"},{"key":"B102","doi-asserted-by":"publisher","DOI":"10.1186\/s12951-025-03654-x"},{"key":"B103","doi-asserted-by":"publisher","DOI":"10.4103\/1673-5374.382254"},{"key":"B104","doi-asserted-by":"publisher","DOI":"10.1007\/s12031-021-01887-7"},{"key":"B105","doi-asserted-by":"publisher","DOI":"10.1002\/ctm2.936"},{"key":"B106","doi-asserted-by":"publisher","DOI":"10.4103\/1673-5374.346466"},{"key":"B107","doi-asserted-by":"publisher","DOI":"10.1093\/stmcls\/sxab026"},{"key":"B108","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2025.1543826"},{"key":"B109","doi-asserted-by":"publisher","DOI":"10.1002\/imo2.33"},{"key":"B110","doi-asserted-by":"publisher","DOI":"10.1080\/19490976.2025.2611546"},{"key":"B111","doi-asserted-by":"publisher","DOI":"10.2147\/ijn.s562305"},{"key":"B112","doi-asserted-by":"publisher","DOI":"10.1002\/jev2.12306"},{"key":"B113","doi-asserted-by":"publisher","DOI":"10.1016\/j.fmre.2023.09.007"},{"key":"B114","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioactmat.2025.09.024"},{"key":"B115","doi-asserted-by":"publisher","DOI":"10.1016\/j.phymed.2026.158232"},{"key":"B116","doi-asserted-by":"publisher","DOI":"10.1186\/s13054-023-04413-w"},{"key":"B117","doi-asserted-by":"publisher","DOI":"10.1021\/acsnano.5c21273"},{"key":"B118","doi-asserted-by":"publisher","DOI":"10.1186\/s12979-019-0150-2"},{"key":"B119","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2024.10.033"},{"key":"B120","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.1807"},{"key":"B121","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2025.116109"},{"key":"B122","doi-asserted-by":"publisher","DOI":"10.3390\/nu18081208"},{"key":"B123","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2025.150003"},{"key":"B124","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-025-02312-w"},{"key":"B125","doi-asserted-by":"publisher","DOI":"10.1016\/j.foodchem.2025.146575"},{"key":"B126","doi-asserted-by":"publisher","DOI":"10.1039\/d4ay01158a"},{"key":"B127","doi-asserted-by":"publisher","DOI":"10.1016\/j.cjprs.2025.05.001"},{"key":"B128","doi-asserted-by":"publisher","DOI":"10.1093\/stcltm\/szaf064"},{"key":"B129","doi-asserted-by":"publisher","DOI":"10.1016\/j.addr.2026.115810"},{"key":"B130","doi-asserted-by":"publisher","DOI":"10.1016\/j.mtbio.2025.101613"},{"key":"B131","doi-asserted-by":"publisher","DOI":"10.1007\/s12017-021-08696-6"},{"key":"B132","doi-asserted-by":"publisher","DOI":"10.1038\/s44328-026-00086-x"},{"key":"B133","doi-asserted-by":"publisher","DOI":"10.1039\/d5bm00377f"},{"key":"B134","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2024.122544"},{"key":"B135","doi-asserted-by":"publisher","DOI":"10.1016\/j.tranon.2024.102121"},{"key":"B136","doi-asserted-by":"publisher","DOI":"10.3390\/photonics11020101"},{"key":"B137","doi-asserted-by":"publisher","DOI":"10.2147\/ijn.s579695"},{"key":"B138","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-50021-9"},{"key":"B139","doi-asserted-by":"publisher","DOI":"10.1038\/s41580-025-00922-4"},{"key":"B140","doi-asserted-by":"publisher","DOI":"10.20517\/evcna.2025.158"},{"key":"B141","doi-asserted-by":"publisher","DOI":"10.1161\/strokeaha.124.048964"},{"key":"B142","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-023-01657-4"},{"key":"B143","doi-asserted-by":"publisher","DOI":"10.1039\/c9nr01255a"},{"key":"B144","doi-asserted-by":"publisher","DOI":"10.1080\/10717544.2020.1762262"},{"key":"B145","doi-asserted-by":"publisher","DOI":"10.2147\/dddt.s417465"},{"key":"B146","doi-asserted-by":"publisher","DOI":"10.1021\/acsnano.3c13150"},{"key":"B147","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.adi4830"},{"key":"B148","doi-asserted-by":"publisher","DOI":"10.1002\/adma.202311420"},{"key":"B149","doi-asserted-by":"publisher","DOI":"10.1002\/jev2.70215"},{"key":"B150","doi-asserted-by":"publisher","DOI":"10.1002\/jev2.70031"},{"key":"B151","doi-asserted-by":"publisher","DOI":"10.1016\/j.jare.2025.08.003"},{"key":"B152","doi-asserted-by":"publisher","DOI":"10.1186\/s12645-025-00334-1"},{"key":"B153","doi-asserted-by":"publisher","DOI":"10.1021\/acs.nanolett.6c01310"},{"key":"B154","doi-asserted-by":"publisher","DOI":"10.1021\/acssensors.5c00827"},{"key":"B155","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-025-63075-0"},{"key":"B156","doi-asserted-by":"publisher","DOI":"10.26599\/nr.2025.94907571"},{"key":"B157","doi-asserted-by":"publisher","DOI":"10.59717\/j.xinn-med.2025.100121"},{"key":"B158","doi-asserted-by":"publisher","DOI":"10.1002\/adma.202509410"},{"key":"B159","doi-asserted-by":"publisher","DOI":"10.1016\/j.omtn.2026.102870"},{"key":"B160","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2026.1834543"},{"key":"B161","doi-asserted-by":"publisher","DOI":"10.20517\/evcna.2025.164"},{"key":"B162","doi-asserted-by":"publisher","DOI":"10.1016\/j.addr.2023.114949"},{"key":"B163","doi-asserted-by":"publisher","DOI":"10.1016\/j.addr.2020.02.006"},{"key":"B164","unstructured":"DDEL-10. Retrospective review of intra-CSF drug delivery: safety and drug distribution profiles of intracerebroventricular (ICV), lumbar intrathecal (LIT), and intra-cisterna magna (ICM) injections"},{"key":"B165","doi-asserted-by":"publisher","DOI":"10.1007\/s13346-021-00940-7"},{"key":"B166","doi-asserted-by":"publisher","DOI":"10.1016\/j.actbio.2026.02.049"},{"key":"B167","doi-asserted-by":"publisher","DOI":"10.1002\/jev2.70110"},{"key":"B168","doi-asserted-by":"publisher","DOI":"10.1186\/s12964-026-02654-0"},{"key":"B169","doi-asserted-by":"publisher","DOI":"10.1016\/j.jare.2025.03.042"},{"key":"B170","doi-asserted-by":"publisher","DOI":"10.1038\/s41565-023-01522-z"},{"key":"B171","doi-asserted-by":"publisher","DOI":"10.1038\/s41570-025-00770-y"},{"key":"B172","doi-asserted-by":"publisher","DOI":"10.4252\/wjsc.v17.i7.107080"},{"key":"B173","doi-asserted-by":"publisher","DOI":"10.1002\/jev2.70116"},{"key":"B174","doi-asserted-by":"publisher","DOI":"10.1002\/adma.202417097"},{"key":"B175","doi-asserted-by":"publisher","DOI":"10.1021\/acsnano.5c20533"},{"key":"B176","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jafc.5c01547"},{"key":"B177","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-46259-y"},{"key":"B178","doi-asserted-by":"publisher","DOI":"10.1136\/gpsych-2023-101143"},{"key":"B179","doi-asserted-by":"publisher","DOI":"10.24659\/gsr.11.3_103"},{"key":"B180","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2026.116658"},{"key":"B181","doi-asserted-by":"publisher","DOI":"10.20517\/and.2024.32"},{"key":"B182","doi-asserted-by":"publisher","DOI":"10.1002\/jev2.70248"},{"key":"B183","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-022-05034-x"},{"key":"B184","doi-asserted-by":"publisher","DOI":"10.1007\/s11095-024-03757-4"}],"container-title":["Extracellular Vesicles and Circulating Nucleic Acids"],"original-title":[],"link":[{"URL":"https:\/\/www.oaepublish.com\/articles\/evcna.2026.43","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.oaepublish.com\/articles\/evcna.2026.43","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T10:37:35Z","timestamp":1785235055000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.oaepublish.com\/articles\/evcna.2026.43"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,28]]},"references-count":184,"journal-issue":{"issue":"3"},"URL":"https:\/\/doi.org\/10.20517\/evcna.2026.43","relation":{},"ISSN":["2767-6641"],"issn-type":[{"value":"2767-6641","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,28]]}}}