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,
{"title":"Plasma miRNAs across the Alzheimer's disease continuum: Relationship to central biomarkers.","authors":"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,","doi":"10.1002/alz.14230","DOIUrl":null,"url":null,"abstract":"INTRODUCTION\r\nMicroRNAs (miRNAs) play important roles in gene expression regulation and Alzheimer's disease (AD) pathogenesis.\r\n\r\nMETHODS\r\nWe 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.\r\n\r\nRESULTS\r\nWe 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.\r\n\r\nDISCUSSION\r\nPlasma miRNAs were associated with central A/T/N biomarkers, highlighting their potential as blood biomarkers.\r\n\r\nHIGHLIGHTS\r\nWe 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.","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":null,"pages":null},"PeriodicalIF":13.0000,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Alzheimer's & Dementia","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1002/alz.14230","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CLINICAL NEUROLOGY","Score":null,"Total":0}
引用次数: 0
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.
期刊介绍:
Alzheimer's & Dementia is a peer-reviewed journal that aims to bridge knowledge gaps in dementia research by covering the entire spectrum, from basic science to clinical trials to social and behavioral investigations. It provides a platform for rapid communication of new findings and ideas, optimal translation of research into practical applications, increasing knowledge across diverse disciplines for early detection, diagnosis, and intervention, and identifying promising new research directions. In July 2008, Alzheimer's & Dementia was accepted for indexing by MEDLINE, recognizing its scientific merit and contribution to Alzheimer's research.