{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T02:07:08Z","timestamp":1793066828048,"version":"4.5.0"},"reference-count":57,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"736","content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Transl. Med."],"published-print":{"date-parts":[[2024,2,28]]},"abstract":"<jats:p>\n            Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune astrocytopathy of the central nervous system, mediated by antibodies against aquaporin-4 water channel protein (AQP4-Abs), resulting in damage of astrocytes with subsequent demyelination and axonal damage. Extracellular communication through astrocyte-derived extracellular vesicles (ADEVs) has received growing interest in association with astrocytopathies. However, to what extent ADEVs contribute to NMOSD pathogenesis remains unclear. Here, through proteomic screening of patient-derived ADEVs, we observed an increase in apolipoprotein E (APOE)\u2013rich ADEVs in patients with AQP4-Abs\u2013positive NMOSD. Intracerebral injection of the APOE-mimetic peptide APOE\n            <jats:sub>130\u2013149<\/jats:sub>\n            attenuated microglial reactivity, neuroinflammation, and brain lesions in a mouse model of NMOSD. The protective effect of APOE in NMOSD pathogenesis was further established by the exacerbated lesion volume in APOE-deficient mice, which could be rescued by exogenous APOE administration. Genetic knockdown of the APOE receptor lipoprotein receptor\u2013related protein 1 (LRP1) could block the restorative effects of APOE\n            <jats:sub>130\u2013149<\/jats:sub>\n            administration. The transfusion ADEVs derived from patients with NMOSD and healthy controls also alleviated astrocyte loss, reactive microgliosis, and demyelination in NMOSD mice. The slightly larger beneficial effect of patient-derived ADEVs as compared to ADEVs from healthy controls was further augmented in APOE\n            <jats:sup>\u2212\/\u2212<\/jats:sup>\n            mice. These results indicate that APOE from astrocyte-derived extracellular vesicles could mediate disease-modifying astrocyte-microglia cross-talk in NMOSD.\n          <\/jats:p>","DOI":"10.1126\/scitranslmed.adg5116","type":"journal-article","created":{"date-parts":[[2024,2,28]],"date-time":"2024-02-28T18:58:34Z","timestamp":1709146714000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":32,"title":["APOE from patient-derived astrocytic extracellular vesicles alleviates neuromyelitis optica spectrum disorder in a mouse model"],"prefix":"10.1126","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8542-2277","authenticated-orcid":true,"given":"Shihe","family":"Jiang","sequence":"first","affiliation":[{"name":"Department of Neurology, China National Clinical Research Center for Neurological Diseases, Beijing Tiantan Hospital, Capital Medical University, Beijing 100070, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-9027-6993","authenticated-orcid":true,"given":"Xindi","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Neurology, China National Clinical Research Center for Neurological Diseases, Beijing Tiantan Hospital, Capital Medical University, Beijing 100070, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0815-3565","authenticated-orcid":true,"given":"Yan","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Neurology, China National Clinical Research Center for Neurological Diseases, Beijing Tiantan Hospital, Capital Medical University, Beijing 100070, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3982-6240","authenticated-orcid":true,"given":"Zhilin","family":"Chang","sequence":"additional","affiliation":[{"name":"Department of 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China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-8476-8379","authenticated-orcid":true,"given":"Hengri","family":"Cong","sequence":"additional","affiliation":[{"name":"Department of Neurology, China National Clinical Research Center for Neurological Diseases, Beijing Tiantan Hospital, Capital Medical University, Beijing 100070, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6159-1639","authenticated-orcid":true,"given":"Linlin","family":"Yin","sequence":"additional","affiliation":[{"name":"Department of Neurology, China National Clinical Research Center for Neurological Diseases, Beijing Tiantan Hospital, Capital Medical University, Beijing 100070, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9532-0100","authenticated-orcid":true,"given":"Zhen-Wei","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Neurology, China National Clinical Research Center for Neurological Diseases, Beijing Tiantan Hospital, Capital Medical University, Beijing 100070, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5305-6097","authenticated-orcid":true,"given":"Junwan","family":"Fan","sequence":"additional","affiliation":[{"name":"Department of Neurology, China National Clinical Research Center for Neurological Diseases, Beijing Tiantan Hospital, Capital Medical University, Beijing 100070, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8752-4768","authenticated-orcid":true,"given":"Wenyan","family":"He","sequence":"additional","affiliation":[{"name":"Department of Neurology, China National Clinical Research Center for Neurological Diseases, Beijing Tiantan Hospital, Capital Medical University, Beijing 100070, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7343-7498","authenticated-orcid":true,"given":"Kaibin","family":"Shi","sequence":"additional","affiliation":[{"name":"Department of Neurology, China National Clinical Research Center for Neurological Diseases, Beijing Tiantan Hospital, Capital Medical University, Beijing 100070, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5153-2491","authenticated-orcid":true,"given":"De-Cai","family":"Tian","sequence":"additional","affiliation":[{"name":"Department of Neurology, China National Clinical Research Center for Neurological Diseases, Beijing Tiantan Hospital, Capital Medical University, Beijing 100070, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7222-8317","authenticated-orcid":true,"given":"Jing","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department 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