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.
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This post is Copyright: Shiwei Liu,
Tamina Park,
Dennis M. Krüger,
Tonatiuh Pena‐Centeno,
Susanne Burkhardt,
Anna‐Lena Schutz,
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,
Andre Fischer,
Kwangsik Nho,
for the Alzheimer’s Disease Neuroimaging Initiative | September 18, 2024