{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T21:22:10Z","timestamp":1791062530188,"version":"4.1.0"},"reference-count":54,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2022,7,2]],"date-time":"2022-07-02T00:00:00Z","timestamp":1656720000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 AG056711"],"award-info":[{"award-number":["R01 AG056711"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["U01 NS091272"],"award-info":[{"award-number":["U01 NS091272"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R21 AG060142"],"award-info":[{"award-number":["R21 AG060142"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R21 NS104511"],"award-info":[{"award-number":["R21 NS104511"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R21\/R33MH118160"],"award-info":[{"award-number":["R21\/R33MH118160"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01AG061383"],"award-info":[{"award-number":["R01AG061383"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["RF1AG068406"],"award-info":[{"award-number":["RF1AG068406"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P50NS062684"],"award-info":[{"award-number":["P50NS062684"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P50AG005136"],"award-info":[{"award-number":["P50AG005136"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002858","name":"China Postdoctoral Science Foundation","doi-asserted-by":"publisher","award":["2021M702829"],"award-info":[{"award-number":["2021M702829"]}],"id":[{"id":"10.13039\/501100002858","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012226","name":"Fundamental Research Funds for the Central Universities","doi-asserted-by":"publisher","award":["2021FZZX005\u201027"],"award-info":[{"award-number":["2021FZZX005\u201027"]}],"id":[{"id":"10.13039\/501100012226","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["alz-journals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Alzheimer's &amp;amp; Dementia"],"published-print":{"date-parts":[[2023,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Introduction<\/jats:title><jats:p>Objective and accessible markers for Alzheimer's disease (AD) and other dementias are critically needed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We identified NMDAR2A, a protein related to synaptic function, as a novel marker of central nervous system (CNS)\u2010derived plasma extracellular vesicles (EVs) and developed a flow cytometry\u2010based technology for detecting such plasma EVs readily. The assay was initially tested in our local cross\u2010sectional study to distinguish AD patients from healthy controls (HCs) or from Parkinson's disease (PD) patients, followed by a validation study using an independent cohort collected from multiple medical centers (the Alzheimer's Disease Neuroimaging Initiative). Cerebrospinal fluid AD molecular signature was used to confirm diagnoses of all AD participants.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Likely CNS\u2010derived EVs in plasma were significantly reduced in AD compared to HCs in both cohorts. Integrative models including CNS\u2010derived EV markers and AD markers present on EVs reached area under the curve of 0.915 in discovery cohort and 0.810 in validation cohort.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>This study demonstrated that robust and rapid analysis of individual neuron\u2010derived synaptic function\u2013related EVs in peripheral blood may serve as a helpful marker of synaptic dysfunction in AD and dementia.<\/jats:p><\/jats:sec>","DOI":"10.1002\/alz.12723","type":"journal-article","created":{"date-parts":[[2022,7,2]],"date-time":"2022-07-02T10:24:08Z","timestamp":1656757448000},"page":"909-923","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":74,"title":["Blood extracellular vesicles carrying synaptic function\u2010 and brain\u2010related proteins as potential biomarkers for Alzheimer's disease"],"prefix":"10.1002","volume":"19","author":[{"given":"Chen","family":"Tian","sequence":"first","affiliation":[{"name":"Department of Pathology First Affiliated Hospital Zhejiang University School of Medicine  Zhejiang China"},{"name":"Department of Laboratory Medicine and Pathology University of Washington School of Medicine  Seattle Washington USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tessandra","family":"Stewart","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathology University of Washington School of Medicine  Seattle Washington USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhen","family":"Hong","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathology University of Washington School of Medicine  Seattle Washington USA"},{"name":"Department of Neurology West China Medical School Sichuan University  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhen","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Pathology First Affiliated Hospital Zhejiang University School of Medicine  Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Aro","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathology University of Washington School of Medicine  Seattle Washington USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Soltys","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathology University of Washington School of Medicine  Seattle Washington USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine","family":"Pan","sequence":"additional","affiliation":[{"name":"Department of Pathology First Affiliated Hospital Zhejiang University School of Medicine  Zhejiang China"},{"name":"Department of Laboratory Medicine and Pathology University of Washington School of Medicine  Seattle Washington USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elaine R","family":"Peskind","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Behavioral Sciences University of Washington School of Medicine  Seattle Washington USA"},{"name":"Northwest (VISN\u201020) Mental Illness Research Education and Clinical Center Veterans Affairs Puget Sound Health Care System  Seattle Washington USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cyrus P.","family":"Zabetian","sequence":"additional","affiliation":[{"name":"Veterans Affairs Puget Sound Health Care System  Seattle Washington USA"},{"name":"Department of Neurology University of Washington School of Medicine  Seattle Washington USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leslie M.","family":"Shaw","sequence":"additional","affiliation":[{"name":"Center for Neurodegenerative Disease Research Perelman School of Medicine at the University of Pennsylvania  Philadelphia Pennsylvania USA"},{"name":"Department of Pathology and Laboratory Medicine Perelman School of Medicine at the University of Pennsylvania  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Douglas","family":"Galasko","sequence":"additional","affiliation":[{"name":"Department of Neurology University of California  San Diego California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph F","family":"Quinn","sequence":"additional","affiliation":[{"name":"Department of Neurology Oregon Health &amp; Science University  Portland Oregon USA"},{"name":"Department of Neurology and Parkinson's Disease Research Education and Clinical Care Center (PADRECC) VA Portland Healthcare System  Portland Oregon USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6901-2558","authenticated-orcid":false,"given":"Min","family":"Shi","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathology University of Washington School of Medicine  Seattle Washington USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pathology First Affiliated Hospital Zhejiang University School of Medicine  Zhejiang China"},{"name":"National Health and Disease Human Brain Tissue Resource Center Zhejiang University  Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"Alzheimer's Disease Neuroimaging Initiative","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,7,2]]},"reference":[{"issue":"3","key":"e_1_2_6_2_1","first-page":"79","article-title":"2021 Alzheimer's Disease Facts and Figures","volume":"17","author":"Association As","year":"2021","journal-title":"Alzheimers Dement"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2018.02.018"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pneurobio.2020.101801"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/alz.12546"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-020-02234-7"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.2174\/1567205017666200224121447"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11064-019-02748-x"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/jev2.12035"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(20)30071-5"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awaa422"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-014-1314-y"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1089\/neu.2019.6711"},{"key":"e_1_2_6_14_1","article-title":"Exosomes as cell\u2010derivative carriers in the diagnosis and treatment of central nervous system diseases","author":"Shetgaonkar GG","year":"2021","journal-title":"Drug Deliv Transl Res"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2016.04.003"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2014.06.008"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.25172"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/jnc.15112"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.arr.2021.101321"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pneurobio.2019.01.005"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2019.2462"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2019.05.002"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13365-018-0695-4"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000011853"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-0173(97)00033-7"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1006\/geno.1997.5132"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41423-020-0421-z"},{"key":"e_1_2_6_28_1","doi-asserted-by":"publisher","DOI":"10.3390\/pharmaceutics12030284"},{"key":"e_1_2_6_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nlm.2019.107154"},{"key":"e_1_2_6_30_1","doi-asserted-by":"publisher","DOI":"10.1097\/WNR.0000000000000260"},{"key":"e_1_2_6_31_1","doi-asserted-by":"publisher","DOI":"10.1002\/alz.12490"},{"key":"e_1_2_6_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2018.01.059"},{"key":"e_1_2_6_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tins.2020.10.014"},{"key":"e_1_2_6_34_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0147-18.2019"},{"key":"e_1_2_6_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.conb.2013.08.005"},{"key":"e_1_2_6_36_1","doi-asserted-by":"publisher","DOI":"10.1002\/1873-3468.14074"},{"key":"e_1_2_6_37_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40035-021-00234-5"},{"key":"e_1_2_6_38_1","doi-asserted-by":"publisher","DOI":"10.1002\/mas.20221"},{"key":"e_1_2_6_39_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.22311"},{"key":"e_1_2_6_40_1","doi-asserted-by":"publisher","DOI":"10.1001\/archneurol.2010.279"},{"key":"e_1_2_6_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2015.05.003"},{"key":"e_1_2_6_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2018.01.010"},{"key":"e_1_2_6_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2010.06.009"},{"key":"e_1_2_6_44_1","doi-asserted-by":"publisher","DOI":"10.1080\/20013078.2018.1535750"},{"key":"e_1_2_6_45_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrneurol.2016.68"},{"key":"e_1_2_6_46_1","doi-asserted-by":"publisher","DOI":"10.1097\/NEN.0000000000000207"},{"key":"e_1_2_6_47_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.R116.757955"},{"key":"e_1_2_6_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.dadm.2016.04.001"},{"key":"e_1_2_6_49_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.201600756R"},{"key":"e_1_2_6_50_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms19030663"},{"key":"e_1_2_6_51_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.201600816R"},{"key":"e_1_2_6_52_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.201700731R"},{"key":"e_1_2_6_53_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-019-1501-x"},{"key":"e_1_2_6_54_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmg.2020.104038"},{"key":"e_1_2_6_55_1","doi-asserted-by":"publisher","DOI":"10.1002\/jev2.12213"}],"container-title":["Alzheimer's &amp; Dementia"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/alz.12723","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/alz.12723","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/alz-journals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/alz.12723","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T12:59:45Z","timestamp":1759928385000},"score":1,"resource":{"primary":{"URL":"https:\/\/alz-journals.onlinelibrary.wiley.com\/doi\/10.1002\/alz.12723"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,7,2]]},"references-count":54,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2023,3]]}},"alternative-id":["10.1002\/alz.12723"],"URL":"https:\/\/doi.org\/10.1002\/alz.12723","archive":["Portico"],"relation":{},"ISSN":["1552-5260","1552-5279"],"issn-type":[{"value":"1552-5260","type":"print"},{"value":"1552-5279","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,7,2]]},"assertion":[{"value":"2021-07-22","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-05-19","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-07-02","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}