Plasma miRNAs across the Alzheimer's disease continuum: Relationship to central biomarkers
Shiwei Liu, Tamina Park, D. Krüger, Tonatiuh Peña Centeno, Susanne Burkhardt, Anna‐Lena Schütz, Yen‐Ning Huang, Thea Rosewood, Soumilee Chaudhuri, MinYoung Cho, Shannon L. Risacher, Yang Wan, Leslie M. Shaw, Farahnaz Sananbenesi, Alexander S. Brodsky, Honghuang Lin, Andre Krunic, Jan Krzysztof Blusztajn, Andrew J. Saykin, Ivana Delalle, André Fischer, Kwangsik Nho, for the Alzheimer's Disease Neuroimaging Initiative
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.