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Differentially expressed miRNAs and their targets were identified, followed by pathway enrichment analysis. Machine learning approaches were applied to investigate the role of miRNAs as blood biomarkers.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p>We identified nine, two, and eight miRNAs significantly associated with A\/T\/N positivity, respectively. We identified 271 genes targeted by amyloid\u2010related miRNAs with estrogen signaling receptor\u2013mediated signaling among the enriched pathways. Additionally, 220 genes targeted by neurodegeneration\u2010related miRNAs showed enrichment in pathways including the insulin growth factor 1 pathway. The classification performance of demographic information for A\/T\/N positivity was increased up to 9% with the inclusion of miRNAs.<\/jats:p><\/jats:sec><jats:sec><jats:title>DISCUSSION<\/jats:title><jats:p>Plasma miRNAs were associated with central A\/T\/N biomarkers, highlighting their potential as blood biomarkers.<\/jats:p><\/jats:sec><jats:sec><jats:title>Highlights<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>We performed association analysis of microRNAs (miRNAs) with amyloid\/tau\/neurodegeneration (A\/T\/N) biomarker positivity.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>We identified dysregulated miRNAs for A\/T\/N biomarker positivity.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>We identified Alzheimer's disease biomarker\u2010specific\/common pathways related to miRNAs.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>miRNAs improved the classification for A\/T\/N positivity by up to 9%.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Our study highlights the potential of miRNAs as blood biomarkers.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec>","DOI":"10.1002\/alz.14230","type":"journal-article","created":{"date-parts":[[2024,9,18]],"date-time":"2024-09-18T07:00:36Z","timestamp":1726642836000},"page":"7698-7714","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["Plasma miRNAs across the Alzheimer's disease continuum: Relationship to central biomarkers"],"prefix":"10.1002","volume":"20","author":[{"given":"Shiwei","family":"Liu","sequence":"first","affiliation":[{"name":"Center for Neuroimaging Department of Radiology and Imaging Sciences Indiana University School of Medicine Indianapolis Indiana USA"},{"name":"Indiana Alzheimer's Disease Research Center Indiana University School of Medicine Indianapolis Indiana 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