{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,6]],"date-time":"2026-09-06T05:12:20Z","timestamp":1788671540505,"version":"build-2803163510"},"reference-count":55,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T00:00:00Z","timestamp":1786492800000},"content-version":"vor","delay-in-days":11,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:00:00Z","timestamp":1785542400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["U54AG065187"],"award-info":[{"award-number":["U54AG065187"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["alz-journals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Alzheimer's & Dementia"],"published-print":{"date-parts":[[2026,8]]},"abstract":"Abstract<\/jats:title>\n \n INTRODUCTION<\/jats:title>\n \n Post mortem<\/jats:italic>\n proteomic analysis of Alzheimer's disease (AD) brain tissue has identified novel target genes and proteins for potential therapeutic development. Moesin (\n MSN<\/jats:italic>\n ) and\n CD44<\/jats:italic>\n were identified as candidate targets. Using human induced pluripotent stem cells (hiPSCs)\u2010derived neurons, we assayed how reducing gene expression of\n MSN<\/jats:italic>\n and\n CD44<\/jats:italic>\n affected amyloid beta secretion, tau phosphorylation, and transcriptional state.\n <\/jats:p>\n <\/jats:sec>\n \n METHODS<\/jats:title>\n \n Knockdown of\n MSN<\/jats:italic>\n and\n CD44<\/jats:italic>\n in hiPSC\u2010derived neurons was performed using short hairpin RNA\u00a0(shRNA). Amyloid precursor protein processing and intracellular tau phosphorylation was measured using chemiluminescent ELISA assays. Global gene expression was analyzed by bulk RNA sequencing (RNA\u2010seq).\n <\/jats:p>\n <\/jats:sec>\n \n RESULTS<\/jats:title>\n \n Knockdown of\n CD44<\/jats:italic>\n and\n MSN<\/jats:italic>\n increased secretion of amyloid beta and soluble APP beta and differentially altered tau generation and phosphorylation. RNA\u2010seq revealed diverse effects of\n CD44<\/jats:italic>\n and\n MSN<\/jats:italic>\n knockdown and the reversal of some expression shifts found in late\u2010onset AD.\n <\/jats:p>\n <\/jats:sec>\n \n DISCUSSION<\/jats:title>\n \n These findings connect reduced\n CD44<\/jats:italic>\n and\n MSN<\/jats:italic>\n expression to AD\u2010related signatures in neurons and inform their role in the disease.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/alz.71734","type":"journal-article","created":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T10:05:40Z","timestamp":1786529140000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Inhibition of\n Moesin<\/i>\n and\n CD44<\/i>\n in stem cell\u2010derived neurons affects the pathological genetic signature associated with Alzheimer's disease"],"prefix":"10.1002","volume":"22","author":[{"given":"Eiden H.","family":"Brewer","sequence":"first","affiliation":[{"name":"Department of Laboratory Medicine and Pathology University of Washington Seattle Washington USA"},{"name":"Institute for Stem Cell and Regenerative Medicine University of Washington Seattle Washington USA"},{"name":"Neurobiology, Neurodegeneration & Repair Laboratory National Eye Institute, National Institutes of Health Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles A.","family":"Williams","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathology University of Washington Seattle Washington USA"},{"name":"Institute for Stem Cell and Regenerative Medicine University of Washington Seattle Washington USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregory A.","family":"Cary","sequence":"additional","affiliation":[{"name":"The Jackson Laboratory Bar Harbor Maine USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ranjita","family":"Betarbet","sequence":"additional","affiliation":[{"name":"Department of Neurology Emory University School of Medicine Atlanta Georgia USA"},{"name":"Emory Goizueta Alzheimer's Disease Research Center Emory University School of Medicine Atlanta Georgia USA"},{"name":"Center for Neurodegenerative Disease Emory University Atlanta Georgia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Inez K. A.","family":"Pranoto","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathology University of Washington Seattle Washington USA"},{"name":"Institute for Stem Cell and Regenerative Medicine University of Washington Seattle Washington USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth L.","family":"Zoeller","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Chemical Biology Emory University School of Medicine Atlanta Georgia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haian","family":"Fu","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Chemical Biology Emory University School of Medicine Atlanta Georgia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Allan I.","family":"Levey","sequence":"additional","affiliation":[{"name":"Department of Neurology Emory University School of Medicine Atlanta Georgia USA"},{"name":"Emory Goizueta Alzheimer's Disease Research Center Emory University School of Medicine Atlanta Georgia USA"},{"name":"Center for Neurodegenerative Disease Emory University Atlanta Georgia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jesse C.","family":"Wiley","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology University of Kansas Lawrence Kansas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregory W.","family":"Carter","sequence":"additional","affiliation":[{"name":"The Jackson Laboratory Bar Harbor Maine USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2106-0339","authenticated-orcid":false,"given":"Jessica E.","family":"Young","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathology University of Washington Seattle Washington USA"},{"name":"Institute for Stem Cell and Regenerative Medicine University of Washington Seattle Washington USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"for the TREAT\u2010AD Consortium","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,12]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/alz.13859"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2212948"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000209218"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/d41586\u2010023\u201000030\u20103"},{"issue":"2","key":"e_1_2_9_6_1","article-title":"Open drug discovery in Alzheimer's disease","volume":"9","author":"Axtman AD","year":"2023","journal-title":"Alzheimers Dement"},{"key":"e_1_2_9_7_1","unstructured":"TREAT\u2010AD centers: Open source tools to reinvigorate Alzheimer's drug discovery | National Institute on Aging [Internet]. 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