{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T11:06:22Z","timestamp":1791975982548,"version":"4.4.0"},"reference-count":36,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2025,6,3]],"date-time":"2025-06-03T00:00:00Z","timestamp":1748908800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100007911","name":"University of California Academic Senate San Diego Division","doi-asserted-by":"publisher","award":["RG104647"],"award-info":[{"award-number":["RG104647"]}],"id":[{"id":"10.13039\/100007911","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Alzheimer\u2019s disease (AD) is a leading cause of dementia worldwide. As current diagnostic approaches remain limited in sensitivity and accessibility, there is a critical need for novel, non-invasive biomarkers aiding early detection. Non-coding RNAs (ncRNAs), including long non-coding RNAs (lncRNAs), PIWI-interacting RNAs (piRNAs), and small nucleolar RNAs (snoRNAs), have emerged as promising candidates due to their regulatory roles in gene expression and association with diseases. In this study, we systematically profiled ncRNA expression from RNA sequencing data of 48 AD and 22 control blood tissue samples, aiming to evaluate their utility as biomarkers for AD classification. Differential expression analysis revealed widespread dysregulation of lncRNAs and piRNAs, with over 5000 lncRNAs and nearly 1000 piRNAs significantly upregulated in AD. Weighted gene co-expression network analysis (WGCNA) identified multiple ncRNA modules associated with the AD phenotype. Using supervised machine learning approaches, we evaluated the diagnostic potential of ncRNA expression profiles, including single-gene, multi-gene, and module-level models. Random Forest models trained on individual genes identified 121 ncRNAs with AUROC &gt; 0.8. Feature importance analysis emphasized ncRNAs such as lnc-MYEF2-3, lnc-PRKACB2, and HBII-115 as major contributors to diagnostic accuracy. These findings support the potential of ncRNA signatures as reliable and non-invasive biomarkers for AD diagnosis.<\/jats:p>","DOI":"10.3390\/biom15060806","type":"journal-article","created":{"date-parts":[[2025,6,3]],"date-time":"2025-06-03T03:57:18Z","timestamp":1748923038000},"page":"806","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Non-Coding RNAs: lncRNA, piRNA, and snoRNA as Robust Plasma Biomarkers of Alzheimer\u2019s Disease"],"prefix":"10.3390","volume":"15","author":[{"given":"Ruomin","family":"Xin","sequence":"first","affiliation":[{"name":"Department of Otolaryngology\u2014Head and Neck Surgery, University of California, La Jolla, San Diego, CA 92093, USA"},{"name":"Research Service, VA San Diego Healthcare System, San Diego, CA 92161, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology\u2014Head and Neck Surgery, University of California, La Jolla, San Diego, CA 92093, USA"},{"name":"Research Service, VA San Diego Healthcare System, San Diego, CA 92161, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0997-2220","authenticated-orcid":false,"given":"Wei Tse","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology\u2014Head and Neck Surgery, University of California, La Jolla, San Diego, CA 92093, USA"},{"name":"Research Service, VA San Diego Healthcare System, San Diego, CA 92161, USA"},{"name":"School of Medicine, University of California, San Francisco, CA 94143, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica","family":"Wang-Rodriguez","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of California, La Jolla, San Diego, CA 92093, USA"},{"name":"Pathology Service, VA San Diego Healthcare System, San Diego, CA 92161, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2790-2480","authenticated-orcid":false,"given":"Weg M.","family":"Ongkeko","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology\u2014Head and Neck Surgery, University of California, La Jolla, San Diego, CA 92093, USA"},{"name":"Research Service, VA San Diego Healthcare System, San Diego, CA 92161, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,3]]},"reference":[{"key":"ref_1","unstructured":"National Institute on Aging (2025, March 31). 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