Rhys E. De Sota, Bojk A. Berghuis, Samantha J. Khoury, Jiali Zhuang, Robert A. Rissman, James B. Brewer, Stephen R. Quake, John J. Sninsky, Shusuke Toden
{"title":"阿尔茨海默病脑脊液转录组分析揭示了与疾病相关的分子失调。","authors":"Rhys E. De Sota, Bojk A. Berghuis, Samantha J. Khoury, Jiali Zhuang, Robert A. Rissman, James B. Brewer, Stephen R. Quake, John J. Sninsky, Shusuke Toden","doi":"10.1002/trc2.70152","DOIUrl":null,"url":null,"abstract":"<div>\n \n \n <section>\n \n <h3> BACKGROUND</h3>\n \n <p>Despite the increasing prevalence of neurodegenerative diseases, the molecular characterization of brain pathologies remains challenging due to limited tissue access. Cerebrospinal fluid (CSF) contains a significant proportion of brain-derived molecular contents, and characterizing these molecules has served as a proxy for evaluating molecular dysregulation in the brain. Here we have characterized the CSF cell-free messenger RNA (cf-mRNA) transcriptome and identified genes and pathways altered in Alzheimer's disease (AD).</p>\n </section>\n \n <section>\n \n <h3> METHODS</h3>\n \n <p>We performed cf-mRNA sequencing on 52 human CSF samples and further compared their transcriptomic profiles to matched plasma samples. In addition, we also investigated the cf-mRNA profiles of CSF in individuals with AD as well as non-cognitively impaired (NCI) controls.</p>\n </section>\n \n <section>\n \n <h3> RESULTS</h3>\n \n <p>The molecular content of CSF cf-mRNA was distinct from that of plasma cf-mRNA, with a substantially higher number of brain-associated genes identified in CSF. A large set of dysregulated gene transcripts from CSF was detected in the AD subjects, and these gene transcripts were able to discriminate AD from NCI subjects. Notably, the gene transcripts were enriched in biological processes closely associated with AD, such as brain development and synaptic signaling. In addition, we discovered a subset of gene transcripts that exhibited a high correlation in matched CSF and plasma samples from AD subjects.</p>\n </section>\n \n <section>\n \n <h3> CONCLUSIONS</h3>\n \n <p>This study not only reveals the novel cf-mRNA content of CSF but also highlights the potential of CSF cf-mRNA profiling as a tool to garner pathophysiological insights into AD.</p>\n </section>\n \n <section>\n \n <h3> Highlights</h3>\n \n <div>\n <ul>\n \n <li>Cell-free messenger RNA (cf-mRNA) sequencing was performed on 52 human cerebrospinal fluid (CSF) samples.</li>\n \n <li>CSF exhibited a distinct transcriptional profile with a higher prevalence of brain-associated genes compared to plasma.</li>\n \n <li>Dysregulated genes in Alzheimer's disease (AD) CSF effectively distinguished AD from non-cognitively impaired controls.</li>\n \n <li>CSF cf-mRNA profiling holds potential as a tool for gaining pathophysiological insights into AD.</li>\n </ul>\n </div>\n </section>\n </div>","PeriodicalId":53225,"journal":{"name":"Alzheimer''s and Dementia: Translational Research and Clinical Interventions","volume":"11 3","pages":""},"PeriodicalIF":6.8000,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12438960/pdf/","citationCount":"0","resultStr":"{\"title\":\"Transcriptome profiling of cerebrospinal fluid in Alzheimer's disease reveals molecular dysregulations associated with disease\",\"authors\":\"Rhys E. De Sota, Bojk A. Berghuis, Samantha J. Khoury, Jiali Zhuang, Robert A. Rissman, James B. Brewer, Stephen R. Quake, John J. Sninsky, Shusuke Toden\",\"doi\":\"10.1002/trc2.70152\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div>\\n \\n \\n <section>\\n \\n <h3> BACKGROUND</h3>\\n \\n <p>Despite the increasing prevalence of neurodegenerative diseases, the molecular characterization of brain pathologies remains challenging due to limited tissue access. Cerebrospinal fluid (CSF) contains a significant proportion of brain-derived molecular contents, and characterizing these molecules has served as a proxy for evaluating molecular dysregulation in the brain. Here we have characterized the CSF cell-free messenger RNA (cf-mRNA) transcriptome and identified genes and pathways altered in Alzheimer's disease (AD).</p>\\n </section>\\n \\n <section>\\n \\n <h3> METHODS</h3>\\n \\n <p>We performed cf-mRNA sequencing on 52 human CSF samples and further compared their transcriptomic profiles to matched plasma samples. In addition, we also investigated the cf-mRNA profiles of CSF in individuals with AD as well as non-cognitively impaired (NCI) controls.</p>\\n </section>\\n \\n <section>\\n \\n <h3> RESULTS</h3>\\n \\n <p>The molecular content of CSF cf-mRNA was distinct from that of plasma cf-mRNA, with a substantially higher number of brain-associated genes identified in CSF. A large set of dysregulated gene transcripts from CSF was detected in the AD subjects, and these gene transcripts were able to discriminate AD from NCI subjects. Notably, the gene transcripts were enriched in biological processes closely associated with AD, such as brain development and synaptic signaling. In addition, we discovered a subset of gene transcripts that exhibited a high correlation in matched CSF and plasma samples from AD subjects.</p>\\n </section>\\n \\n <section>\\n \\n <h3> CONCLUSIONS</h3>\\n \\n <p>This study not only reveals the novel cf-mRNA content of CSF but also highlights the potential of CSF cf-mRNA profiling as a tool to garner pathophysiological insights into AD.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Highlights</h3>\\n \\n <div>\\n <ul>\\n \\n <li>Cell-free messenger RNA (cf-mRNA) sequencing was performed on 52 human cerebrospinal fluid (CSF) samples.</li>\\n \\n <li>CSF exhibited a distinct transcriptional profile with a higher prevalence of brain-associated genes compared to plasma.</li>\\n \\n <li>Dysregulated genes in Alzheimer's disease (AD) CSF effectively distinguished AD from non-cognitively impaired controls.</li>\\n \\n <li>CSF cf-mRNA profiling holds potential as a tool for gaining pathophysiological insights into AD.</li>\\n </ul>\\n </div>\\n </section>\\n </div>\",\"PeriodicalId\":53225,\"journal\":{\"name\":\"Alzheimer''s and Dementia: Translational Research and Clinical Interventions\",\"volume\":\"11 3\",\"pages\":\"\"},\"PeriodicalIF\":6.8000,\"publicationDate\":\"2025-09-16\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12438960/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Alzheimer''s and Dementia: Translational Research and Clinical Interventions\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://alz-journals.onlinelibrary.wiley.com/doi/10.1002/trc2.70152\",\"RegionNum\":0,\"RegionCategory\":null,\"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 and Dementia: Translational Research and Clinical Interventions","FirstCategoryId":"1085","ListUrlMain":"https://alz-journals.onlinelibrary.wiley.com/doi/10.1002/trc2.70152","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CLINICAL NEUROLOGY","Score":null,"Total":0}
Transcriptome profiling of cerebrospinal fluid in Alzheimer's disease reveals molecular dysregulations associated with disease
BACKGROUND
Despite the increasing prevalence of neurodegenerative diseases, the molecular characterization of brain pathologies remains challenging due to limited tissue access. Cerebrospinal fluid (CSF) contains a significant proportion of brain-derived molecular contents, and characterizing these molecules has served as a proxy for evaluating molecular dysregulation in the brain. Here we have characterized the CSF cell-free messenger RNA (cf-mRNA) transcriptome and identified genes and pathways altered in Alzheimer's disease (AD).
METHODS
We performed cf-mRNA sequencing on 52 human CSF samples and further compared their transcriptomic profiles to matched plasma samples. In addition, we also investigated the cf-mRNA profiles of CSF in individuals with AD as well as non-cognitively impaired (NCI) controls.
RESULTS
The molecular content of CSF cf-mRNA was distinct from that of plasma cf-mRNA, with a substantially higher number of brain-associated genes identified in CSF. A large set of dysregulated gene transcripts from CSF was detected in the AD subjects, and these gene transcripts were able to discriminate AD from NCI subjects. Notably, the gene transcripts were enriched in biological processes closely associated with AD, such as brain development and synaptic signaling. In addition, we discovered a subset of gene transcripts that exhibited a high correlation in matched CSF and plasma samples from AD subjects.
CONCLUSIONS
This study not only reveals the novel cf-mRNA content of CSF but also highlights the potential of CSF cf-mRNA profiling as a tool to garner pathophysiological insights into AD.
Highlights
Cell-free messenger RNA (cf-mRNA) sequencing was performed on 52 human cerebrospinal fluid (CSF) samples.
CSF exhibited a distinct transcriptional profile with a higher prevalence of brain-associated genes compared to plasma.
Dysregulated genes in Alzheimer's disease (AD) CSF effectively distinguished AD from non-cognitively impaired controls.
CSF cf-mRNA profiling holds potential as a tool for gaining pathophysiological insights into AD.
期刊介绍：
Alzheimer''s & Dementia: Translational Research & Clinical Interventions (TRCI) is a peer-reviewed, open access,journal from the Alzheimer''s Association®. The journal seeks to bridge the full scope of explorations between basic research on drug discovery and clinical studies, validating putative therapies for aging-related chronic brain conditions that affect cognition, motor functions, and other behavioral or clinical symptoms associated with all forms dementia and Alzheimer''s disease. The journal will publish findings from diverse domains of research and disciplines to accelerate the conversion of abstract facts into practical knowledge: specifically, to translate what is learned at the bench into bedside applications. The journal seeks to publish articles that go beyond a singular emphasis on either basic drug discovery research or clinical research. Rather, an important theme of articles will be the linkages between and among the various discrete steps in the complex continuum of therapy development. For rapid communication among a multidisciplinary research audience involving the range of therapeutic interventions, TRCI will consider only original contributions that include feature length research articles, systematic reviews, meta-analyses, brief reports, narrative reviews, commentaries, letters, perspectives, and research news that would advance wide range of interventions to ameliorate symptoms or alter the progression of chronic neurocognitive disorders such as dementia and Alzheimer''s disease. The journal will publish on topics related to medicine, geriatrics, neuroscience, neurophysiology, neurology, psychiatry, clinical psychology, bioinformatics, pharmaco-genetics, regulatory issues, health economics, pharmacoeconomics, and public health policy as these apply to preclinical and clinical research on therapeutics.
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
