한빛사논문
Shiwei Liu 1 2 †, Tamina Park 1 2 †, Dennis M Krüger 3 4 †, Tonatiuh Pena-Centeno 3 4 †, Susanne Burkhardt 3, Anna-Lena Schutz 5, Yen-Ning Huang 1 2, Thea Rosewood 1 2, Soumilee Chaudhuri 1 2, MinYoung Cho 1 2, Shannon L Risacher 1 2, Yang Wan 6, Leslie M Shaw 6, Farahnaz Sananbenesi 5, Alexander S Brodsky 7, Honghuang Lin 8, Andre Krunic 9, Jan Krzysztof Blusztajn 9, Andrew J Saykin 1 2, Ivana Delalle 9, Andre Fischer 3 10 11 12 *, Kwangsik Nho 1 2 13 *; Alzheimer's Disease Neuroimaging Initiative
1Center for Neuroimaging, Department of Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, Indiana, USA.
2Indiana Alzheimer's Disease Research Center, Indiana University School of Medicine, Indianapolis, Indiana, USA.
3Department for Epigenetics and Systems Medicine in Neurodegenerative Diseases, German Center for Neurodegenerative Diseases (DZNE), Göttingen, Germany.
4Bioinformatics Unit, German Center for Neurodegenerative Diseases (DZNE), Göttingen, Germany.
5Research Group for Genome Dynamics in Neurodegenerative Diseases, German Center for Neurodegenerative Diseases (DZNE), Göttingen, Germany.
6Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
7Department of Pathology and Laboratory Medicine, Rhode Island Hospital, Warren Alpert Medical School at Brown University, Providence, Rhode Island, USA.
8Department of Medicine, UMass Chan Medical School, Worcester, Massachusetts, USA.
9Department of Pathology & Laboratory Medicine, Boston University Chobanian & Avedisian School of Medicine, Boston, Massachusetts, USA.
10Department for Psychiatry and Psychotherapy, University Medical Center of Göttingen, Georg-August University, Göttingen, Germany.
11Cluster of Excellence "Multiscale Bioimaging: from Molecular Machines to Networks of Excitable Cells" (MBExC), University of Göttingen, Göttingen, Germany.
12German Center for Cardiovascular Diseases (DZHK), Göttingen, Germany.
13Center for Computational Biology and Bioinformatics, Indiana University School of Medicine, Indianapolis, Indiana, USA.
†Shiwei Liu, Tamina Park, Dennis M. Krüger, and Tonatiuh Pena-Centeno contributed equally to this work.
*Corresponding authors: correspondence to Andre Fischer or Kwangsik Nho
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.
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