{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T23:18:14Z","timestamp":1784243894267,"version":"3.55.0"},"reference-count":22,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2024,9,14]],"date-time":"2024-09-14T00:00:00Z","timestamp":1726272000000},"content-version":"vor","delay-in-days":75,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["U24 AG021886"],"award-info":[{"award-number":["U24 AG021886"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["1R41AG076098\u201001"],"award-info":[{"award-number":["1R41AG076098\u201001"]}],"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":["1R43AG080878\u201001"],"award-info":[{"award-number":["1R43AG080878\u201001"]}],"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":["2R44GM144009\u201002"],"award-info":[{"award-number":["2R44GM144009\u201002"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["alz-journals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Alz &amp;amp; Dem Diag Ass &amp;amp; Dis Mo"],"published-print":{"date-parts":[[2024,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>INTRODUCTION<\/jats:title><jats:p>Alzheimer's disease (AD), the most prevalent neurodegenerative disorder globally, has emerged as a significant health concern. Recently it has been revealed that extracellular vesicles (EVs) play a critical role in AD pathogenesis and progression. Their stability and presence in various biofluids, such as blood, offer a minimally invasive window for monitoring AD\u2010related changes.<\/jats:p><\/jats:sec><jats:sec><jats:title>METHODS<\/jats:title><jats:p>We analyzed plasma EV\u2010derived messenger RNA (mRNA) from 82 human subjects, including individuals with AD, mild cognitive impairment (MCI), and healthy controls. With next\u2010generation sequencing, we profiled differentially expressed genes (DEGs), identifying those associated with AD.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p>Based on DEGs identified in both the MCI and AD groups, a diagnostic model was established based on machine learning, demonstrating an average diagnostic accuracy of over 98% and showed a strong correlation with different AD stages.<\/jats:p><\/jats:sec><jats:sec><jats:title>DISCUSSION<\/jats:title><jats:p>mRNA derived from plasma EVs shows significant promise as a non\u2010invasive biomarker for the early detection and continuous monitoring of AD.<\/jats:p><\/jats:sec><jats:sec><jats:title>Highlights<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>The study conducted next\u2010generation sequencing (NGS) of mRNA derived from human plasma extracellular vesicles (EVs) to assess Alzheimer's disease (AD).<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Profiling of plasma EV\u2010derived mRNA shows a significantly enriched AD pathway, indicating its potential for AD\u2010related studies.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>The AD\u2010prediction model achieved a receiver\u2010operating characteristic area under the curve (ROC\u2010AUC) of more than 0.98, with strong correlation to the established Clinical Dementia Rating (CDR).<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec>","DOI":"10.1002\/dad2.70006","type":"journal-article","created":{"date-parts":[[2024,9,14]],"date-time":"2024-09-14T05:55:25Z","timestamp":1726293325000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Assessing Alzheimer's disease via plasma extracellular vesicle\u2013derived mRNA"],"prefix":"10.1002","volume":"16","author":[{"given":"Le Hoang Phu","family":"Pham","sequence":"first","affiliation":[{"name":"WellSIM Biomedical Technologies Inc.  San Jose California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ching\u2010Fang","family":"Chang","sequence":"additional","affiliation":[{"name":"WellSIM Biomedical Technologies Inc.  San Jose California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine","family":"Tuchez","sequence":"additional","affiliation":[{"name":"WellSIM Biomedical Technologies Inc.  San Jose California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fei","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Medicine Brigham and Women's Hospital Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuchao","family":"Chen","sequence":"additional","affiliation":[{"name":"WellSIM Biomedical Technologies Inc.  San Jose California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,9,14]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1001\/archneur.58.3.397"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/978\u20103\u20107091\u20107508\u20108_3"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010020\u201062378\u20100"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.14283\/jpad.2021.23"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0733\u20108619(05)70368\u20106"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13024\u2010019\u20100317\u20105"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/alz.12723"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awaa376"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12017\u2010022\u201008704\u20103"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mad.2019.111175"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20071728"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2020.622579"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.3390\/genes12081171"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41580\u2010020\u20100251\u2010y"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2021.620498"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2022.785741"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.14336\/AD.2022.0607"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41592\u2010020\u201001034\u2010x"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bios.2023.115088"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsnano.3c00922"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1177\/1740774518816323"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.3233\/JAD\u20102011\u20100062"}],"container-title":["Alzheimer's &amp; Dementia: Diagnosis, Assessment &amp; Disease Monitoring"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/alz-journals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/dad2.70006","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T10:53:08Z","timestamp":1760352788000},"score":1,"resource":{"primary":{"URL":"https:\/\/alz-journals.onlinelibrary.wiley.com\/doi\/10.1002\/dad2.70006"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,7]]},"references-count":22,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2024,7]]}},"alternative-id":["10.1002\/dad2.70006"],"URL":"https:\/\/doi.org\/10.1002\/dad2.70006","archive":["Portico"],"relation":{},"ISSN":["2352-8729","2352-8729"],"issn-type":[{"value":"2352-8729","type":"print"},{"value":"2352-8729","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,7]]},"assertion":[{"value":"2024-03-19","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-08-20","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-09-14","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70006"}}