Liu, ShiweiPark, TaminaKrüger, Dennis M.Pena-Centeno, TonatiuhBurkhardt, SusanneSchutz, Anna-LenaHuang, Yen-NingRosewood, TheaChaudhuri, SoumileeCho, MinYoungRisacher, Shannon L.Wan, YangShaw, Leslie M.Sananbenesi, FarahnazBrodsky, Alexander S.Lin, HonghuangKrunic, AndreKrzysztof Blusztajn, JanSaykin, Andrew J.Delalle, IvanaFischer, AndreNho, KwangsikAlzheimer's Disease Neuroimaging Initiative2024-12-092024-12-092024Liu S, Park T, Krüger DM, et al. Plasma miRNAs across the Alzheimer's disease continuum: Relationship to central biomarkers. Alzheimers Dement. 2024;20(11):7698-7714. doi:10.1002/alz.14230https://hdl.handle.net/1805/44844Introduction: MicroRNAs (miRNAs) play important roles in gene expression regulation and Alzheimer's disease (AD) pathogenesis. Methods: We investigated the association between baseline plasma miRNAs and central AD biomarkers from the Alzheimer's Disease Neuroimaging Initiative (ADNI; N = 803): amyloid, tau, and neurodegeneration (A/T/N). 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. Results: We identified nine, two, and eight miRNAs significantly associated with A/T/N positivity, respectively. We identified 271 genes targeted by amyloid-related miRNAs with estrogen signaling receptor-mediated signaling among the enriched pathways. Additionally, 220 genes targeted by neurodegeneration-related 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. Discussion: Plasma miRNAs were associated with central A/T/N biomarkers, highlighting their potential as blood biomarkers. Highlights: We performed association analysis of microRNAs (miRNAs) with amyloid/tau/neurodegeneration (A/T/N) biomarker positivity. We identified dysregulated miRNAs for A/T/N biomarker positivity. We identified Alzheimer's disease biomarker-specific/common pathways related to miRNAs. miRNAs improved the classification for A/T/N positivity by up to 9%. Our study highlights the potential of miRNAs as blood biomarkers.en-USAttribution-NonCommercial-NoDerivatives 4.0 InternationalAlzheimer's diseaseAmyloidBiomarkersClassificationMicroRNAsNeurodegenerationPlasmaTauArticle