دورية أكاديمية
أعرض في EDS

Huntington's disease blood and brain show a common gene expression pattern and share an immune signature with Alzheimer's disease.

التفاصيل البيبلوغرافية
العنوان: Huntington's disease blood and brain show a common gene expression pattern and share an immune signature with Alzheimer's disease.
المؤلفون: Hensman Moss DJ; Department of Neurodegenerative Disease, University College London Institute of Neurology, London, WC1B 5EH, UK., Flower MD; Department of Neurodegenerative Disease, University College London Institute of Neurology, London, WC1B 5EH, UK., Lo KK; University College London Genetics Institute, University College London, London, WC1E 6BT, UK., Miller JR; Department of Neurodegenerative Disease, University College London Institute of Neurology, London, WC1B 5EH, UK., van Ommen GB; Department of Human Genetics, Leiden University Medical Center, Leiden, Postzone S-4-P, The Netherlands., 't Hoen PA; Department of Human Genetics, Leiden University Medical Center, Leiden, Postzone S-4-P, The Netherlands., Stone TC; MRC Centre for Neuropsychiatric Genetics and Genomics, School of Medicine, Cardiff University, CF24 4HQ, UK., Guinee A; Faculty of Education, University of Cambridge, CB2 8PQ, Cambridge UK., Langbehn DR; Departments of Psychiatry and Biostatistics, University of Iowa, IA 52242, USA., Jones L; MRC Centre for Neuropsychiatric Genetics and Genomics, School of Medicine, Cardiff University, CF24 4HQ, UK., Plagnol V; University College London Genetics Institute, University College London, London, WC1E 6BT, UK., van Roon-Mom WM; Department of Human Genetics, Leiden University Medical Center, Leiden, Postzone S-4-P, The Netherlands., Holmans P; MRC Centre for Neuropsychiatric Genetics and Genomics, School of Medicine, Cardiff University, CF24 4HQ, UK., Tabrizi SJ; Department of Neurodegenerative Disease, University College London Institute of Neurology, London, WC1B 5EH, UK.
المصدر: Scientific reports [Sci Rep] 2017 Mar 21; Vol. 7, pp. 44849. Date of Electronic Publication: 2017 Mar 21.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Nature Publishing Group Country of Publication: England NLM ID: 101563288 Publication Model: Electronic Cited Medium: Internet ISSN: 2045-2322 (Electronic) Linking ISSN: 20452322 NLM ISO Abbreviation: Sci Rep Subsets: MEDLINE
أسماء مطبوعة: Original Publication: London : Nature Publishing Group, copyright 2011-
مواضيع طبية MeSH: Gene Expression Regulation* , Transcriptome*, Alzheimer Disease/*etiology , Brain/*metabolism , Huntington Disease/*etiology , Immunity/*genetics, Adult ; Aged ; Alzheimer Disease/blood ; Alzheimer Disease/diagnosis ; Alzheimer Disease/metabolism ; Biomarkers ; Case-Control Studies ; Female ; Gene Expression Profiling ; Gene Regulatory Networks ; High-Throughput Nucleotide Sequencing ; Humans ; Huntington Disease/blood ; Huntington Disease/diagnosis ; Huntington Disease/metabolism ; Male ; Middle Aged ; Myeloid Cells/immunology ; Myeloid Cells/metabolism ; Prefrontal Cortex/metabolism ; Signal Transduction ; Young Adult
مستخلص: There is widespread transcriptional dysregulation in Huntington's disease (HD) brain, but analysis is inevitably limited by advanced disease and postmortem changes. However, mutant HTT is ubiquitously expressed and acts systemically, meaning blood, which is readily available and contains cells that are dysfunctional in HD, could act as a surrogate for brain tissue. We conducted an RNA-Seq transcriptomic analysis using whole blood from two HD cohorts, and performed gene set enrichment analysis using public databases and weighted correlation network analysis modules from HD and control brain datasets. We identified dysregulated gene sets in blood that replicated in the independent cohorts, correlated with disease severity, corresponded to the most significantly dysregulated modules in the HD caudate, the most prominently affected brain region, and significantly overlapped with the transcriptional signature of HD myeloid cells. High-throughput sequencing technologies and use of gene sets likely surmounted the limitations of previously inconsistent HD blood expression studies. Our results suggest transcription is disrupted in peripheral cells in HD through mechanisms that parallel those in brain. Immune upregulation in HD overlapped with Alzheimer's disease, suggesting a common pathogenic mechanism involving macrophage phagocytosis and microglial synaptic pruning, and raises the potential for shared therapeutic approaches.
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معلومات مُعتمدة: MR/L010305/1 United Kingdom MRC_ Medical Research Council; United Kingdom BB_ Biotechnology and Biological Sciences Research Council; MR/P007015/1 United Kingdom MRC_ Medical Research Council; 200181/Z/15/Z United Kingdom WT_ Wellcome Trust; MR/L02053X/1 United Kingdom MRC_ Medical Research Council; MR/J003832/1 United Kingdom MRC_ Medical Research Council
المشرفين على المادة: 0 (Biomarkers)
تواريخ الأحداث: Date Created: 20170322 Date Completed: 20181114 Latest Revision: 20240508
رمز التحديث: 20240508
مُعرف محوري في PubMed: PMC5359597
DOI: 10.1038/srep44849
PMID: 28322270
قاعدة البيانات: MEDLINE
الوصف
تدمد:2045-2322
DOI:10.1038/srep44849