Scott E. Counts, John S. Beck, Bryan Maloney, Michael Malek-Ahmadi, Stephen D. Ginsberg, Elliott J. Mufson, Debomoy K. Lahiri
{"title":"后扣带皮层microRNA失调可区分认知弹性、轻度认知障碍和阿尔茨海默病","authors":"Scott E. Counts, John S. Beck, Bryan Maloney, Michael Malek-Ahmadi, Stephen D. Ginsberg, Elliott J. Mufson, Debomoy K. Lahiri","doi":"10.1002/alz.70019","DOIUrl":null,"url":null,"abstract":"<div>\n \n \n <section>\n \n <h3> INTRODUCTION</h3>\n \n <p>MicroRNA (miRNA) activity is increasingly appreciated as a key regulator of pathophysiologic pathways in Alzheimer's disease (AD). However, the role of miRNAs during the progression of AD, including resilience and prodromal syndromes such as mild cognitive impairment (MCI), remains underexplored.</p>\n </section>\n \n <section>\n \n <h3> METHODS</h3>\n \n <p>We performed miRNA-sequencing on samples of posterior cingulate cortex (PCC) obtained <i>post mortem</i> from Rush Religious Orders Study participants diagnosed <i>ante mortem</i> with no cognitive impairment (NCI), MCI, or AD. NCI subjects were subdivided as low pathology (Braak stage I/II) or high pathology (Braak stage III/IV), suggestive of resilience. Bioinformatics approaches included differential expression, messenger RNA (mRNA) target prediction, interactome modeling, functional enrichment, and AD risk modeling.</p>\n </section>\n \n <section>\n \n <h3> RESULTS</h3>\n \n <p>We identified specific miRNA groups, mRNA targets, and signaling pathways distinguishing AD, MCI, resilience, <i>ante mortem</i> neuropsychological test performance, <i>post mortem</i> neuropathological burden, and AD risk.</p>\n </section>\n \n <section>\n \n <h3> DISCUSSION</h3>\n \n <p>These findings highlight the potential of harnessing miRNA activity to manipulate disease-modifying pathways in AD, with implications for precision medicine.</p>\n </section>\n \n <section>\n \n <h3> Highlights</h3>\n \n <div>\n <ul>\n \n <li>MicroRNA (MiRNA) dysregulation is a well-established feature of Alzheimer's disease (AD).</li>\n \n <li>Novel miRNAs also distinguish subjects with mild cognitive impairment and putative resilience.</li>\n \n <li>MiRNAs correlate with cognitive performance and neuropathological burden.</li>\n \n <li>Select miRNAs are associated with AD risk with age as a significant covariate.</li>\n \n <li>MiRNA pathways include insulin, prolactin, kinases, and neurite plasticity.</li>\n </ul>\n </div>\n </section>\n </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 2","pages":""},"PeriodicalIF":11.1000,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70019","citationCount":"0","resultStr":"{\"title\":\"Posterior cingulate cortex microRNA dysregulation differentiates cognitive resilience, mild cognitive impairment, and Alzheimer's disease\",\"authors\":\"Scott E. Counts, John S. Beck, Bryan Maloney, Michael Malek-Ahmadi, Stephen D. Ginsberg, Elliott J. Mufson, Debomoy K. Lahiri\",\"doi\":\"10.1002/alz.70019\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div>\\n \\n \\n <section>\\n \\n <h3> INTRODUCTION</h3>\\n \\n <p>MicroRNA (miRNA) activity is increasingly appreciated as a key regulator of pathophysiologic pathways in Alzheimer's disease (AD). However, the role of miRNAs during the progression of AD, including resilience and prodromal syndromes such as mild cognitive impairment (MCI), remains underexplored.</p>\\n </section>\\n \\n <section>\\n \\n <h3> METHODS</h3>\\n \\n <p>We performed miRNA-sequencing on samples of posterior cingulate cortex (PCC) obtained <i>post mortem</i> from Rush Religious Orders Study participants diagnosed <i>ante mortem</i> with no cognitive impairment (NCI), MCI, or AD. NCI subjects were subdivided as low pathology (Braak stage I/II) or high pathology (Braak stage III/IV), suggestive of resilience. Bioinformatics approaches included differential expression, messenger RNA (mRNA) target prediction, interactome modeling, functional enrichment, and AD risk modeling.</p>\\n </section>\\n \\n <section>\\n \\n <h3> RESULTS</h3>\\n \\n <p>We identified specific miRNA groups, mRNA targets, and signaling pathways distinguishing AD, MCI, resilience, <i>ante mortem</i> neuropsychological test performance, <i>post mortem</i> neuropathological burden, and AD risk.</p>\\n </section>\\n \\n <section>\\n \\n <h3> DISCUSSION</h3>\\n \\n <p>These findings highlight the potential of harnessing miRNA activity to manipulate disease-modifying pathways in AD, with implications for precision medicine.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Highlights</h3>\\n \\n <div>\\n <ul>\\n \\n <li>MicroRNA (MiRNA) dysregulation is a well-established feature of Alzheimer's disease (AD).</li>\\n \\n <li>Novel miRNAs also distinguish subjects with mild cognitive impairment and putative resilience.</li>\\n \\n <li>MiRNAs correlate with cognitive performance and neuropathological burden.</li>\\n \\n <li>Select miRNAs are associated with AD risk with age as a significant covariate.</li>\\n \\n <li>MiRNA pathways include insulin, prolactin, kinases, and neurite plasticity.</li>\\n </ul>\\n </div>\\n </section>\\n </div>\",\"PeriodicalId\":7471,\"journal\":{\"name\":\"Alzheimer's & Dementia\",\"volume\":\"21 2\",\"pages\":\"\"},\"PeriodicalIF\":11.1000,\"publicationDate\":\"2025-02-26\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70019\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Alzheimer's & Dementia\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://alz-journals.onlinelibrary.wiley.com/doi/10.1002/alz.70019\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"CLINICAL NEUROLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Alzheimer's & Dementia","FirstCategoryId":"3","ListUrlMain":"https://alz-journals.onlinelibrary.wiley.com/doi/10.1002/alz.70019","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CLINICAL NEUROLOGY","Score":null,"Total":0}
MicroRNA (miRNA) activity is increasingly appreciated as a key regulator of pathophysiologic pathways in Alzheimer's disease (AD). However, the role of miRNAs during the progression of AD, including resilience and prodromal syndromes such as mild cognitive impairment (MCI), remains underexplored.
METHODS
We performed miRNA-sequencing on samples of posterior cingulate cortex (PCC) obtained post mortem from Rush Religious Orders Study participants diagnosed ante mortem with no cognitive impairment (NCI), MCI, or AD. NCI subjects were subdivided as low pathology (Braak stage I/II) or high pathology (Braak stage III/IV), suggestive of resilience. Bioinformatics approaches included differential expression, messenger RNA (mRNA) target prediction, interactome modeling, functional enrichment, and AD risk modeling.
RESULTS
We identified specific miRNA groups, mRNA targets, and signaling pathways distinguishing AD, MCI, resilience, ante mortem neuropsychological test performance, post mortem neuropathological burden, and AD risk.
DISCUSSION
These findings highlight the potential of harnessing miRNA activity to manipulate disease-modifying pathways in AD, with implications for precision medicine.
Highlights
MicroRNA (MiRNA) dysregulation is a well-established feature of Alzheimer's disease (AD).
Novel miRNAs also distinguish subjects with mild cognitive impairment and putative resilience.
MiRNAs correlate with cognitive performance and neuropathological burden.
Select miRNAs are associated with AD risk with age as a significant covariate.
MiRNA pathways include insulin, prolactin, kinases, and neurite plasticity.
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.
京公网安备 11010802042870号
京ICP备2023020795号-1
分享
求助内容：
应助结果提醒方式：
扫码关注我们
