{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T17:38:43Z","timestamp":1791049123861,"version":"4.1.0"},"reference-count":94,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,26]],"date-time":"2026-05-26T00:00:00Z","timestamp":1779753600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurosci."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Microglia, the resident immune cells of the central nervous system, play a critical role in maintaining neural homeostasis and regulating inflammatory responses in the brain. Increasing evidence suggests that microglial dysfunction contributes to the progression of neurodegenerative diseases, including Alzheimer\u2019s disease (AD). However, the molecular mechanisms underlying these alterations remain incompletely understood. This study aimed to characterize disease-associated molecular changes in microglia derived from induced pluripotent stem cells (iPSCs) of sporadic AD patients and healthy donors.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>iPSC-derived microglia from sporadic AD patients and healthy controls were analyzed using integrated multi-omics approaches, including total RNA sequencing, proteomics, and small non-coding RNA (sncRNA) sequencing. Gene Ontology (GO) analysis was performed to identify dysregulated biological pathways from transcriptomic and proteomic datasets. In addition, a modified T4 polynucleotide kinase (T4 PNK)-based sncRNA sequencing method was used to profile disease-associated sncRNAs and identify previously uncharacterized RNA species.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Comparative analyses revealed significant AD-associated alterations in mRNA, protein, and sncRNA expression profiles in iPSC-derived microglia. GO analysis demonstrated dysregulation of pathways related to extracellular communication, intracellular transport, cytoskeletal organization, and protein\u2013protein interactions. Furthermore, the modified T4 PNK\u2013sncRNA sequencing approach identified multiple disease-associated sncRNAs, including several novel and previously uncharacterized RNA species potentially linked to AD pathology.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>These findings demonstrate that iPSC-derived microglia provide a valuable model for studying molecular mechanisms associated with sporadic AD. The identified transcriptomic, proteomic, and sncRNA alterations highlight key pathways potentially involved in microglial dysfunction and neurodegeneration. In particular, the discovery of novel disease-associated sncRNAs may provide new insights into AD pathogenesis and reveal potential therapeutic targets for future investigation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fnins.2026.1799542","type":"journal-article","created":{"date-parts":[[2026,5,26]],"date-time":"2026-05-26T06:04:33Z","timestamp":1779775473000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Disease-associated RNA and protein signatures in iPSC-derived microglia model of Alzheimer\u2019s disease"],"prefix":"10.3389","volume":"20","author":[{"given":"Wenzhe","family":"Wu","sequence":"first","affiliation":[{"name":"Department of Pediatrics, University of Texas Medical Branch","place":["Galveston, TX, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eun Seok","family":"Choi","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Texas Medical Branch","place":["Galveston, TX, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luke","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Computer Science, University of Rochester","place":["Rochester, NY, United States"]},{"name":"miRcore","place":["Ann Arbor, MI, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veena","family":"Thamilselvan","sequence":"additional","affiliation":[{"name":"miRcore","place":["Ann Arbor, MI, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Le","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Mathematics, College of Natural Sciences, The University of Texas at Austin","place":["Austin, TX, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meagan D.","family":"Rippee-Brooks","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Texas Medical Branch","place":["Galveston, TX, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kashish","family":"Khatkar","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Texas Medical Branch","place":["Galveston, TX, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dar-Yin","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Texas Medical Branch","place":["Galveston, TX, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Denise","family":"McGrath","sequence":"additional","affiliation":[{"name":"RealSeq Biosciences","place":["Santa Cruz, CA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aidan","family":"Manning","sequence":"additional","affiliation":[{"name":"RealSeq Biosciences","place":["Santa Cruz, CA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergio","family":"Barberan-Soler","sequence":"additional","affiliation":[{"name":"RealSeq Biosciences","place":["Santa Cruz, CA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Inhan","family":"Lee","sequence":"additional","affiliation":[{"name":"miRcore","place":["Ann Arbor, MI, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingxin","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University of Texas Medical Branch","place":["Galveston, TX, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiang","family":"Fang","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of Texas Medical Branch","place":["Galveston, TX, United States"]},{"name":"Moody Brain Health Institute, University of Texas Medical Branch","place":["Galveston, TX, United States"]},{"name":"Institute for Translational Science, University of Texas Medical Branch","place":["Galveston, TX, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyong","family":"Bao","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Texas Medical Branch","place":["Galveston, TX, United States"]},{"name":"Institute for Translational Science, University of Texas Medical Branch","place":["Galveston, TX, United States"]},{"name":"Institute for Human Infections & Immunity, University of Texas Medical Branch","place":["Galveston, TX, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,5,26]]},"reference":[{"key":"B1","first-page":"365","article-title":"microRNA (miRNA) speciation in Alzheimer\u2019s disease (AD) cerebrospinal fluid (CSF) and extracellular fluid (ECF).","volume":"3","author":"Alexandrov","year":"2012","journal-title":"Int. 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