Plasma miRNAs across the Alzheimer's disease continuum: Relationship to central biomarkers

Abstract INTRODUCTION 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.