Journal article
Huntington’s disease blood and brain show a common gene expression pattern and share an immune signature with Alzheimer’s disease
Scientific reports, Vol.7(1), pp.44849-44849
03/21/2017
DOI: 10.1038/srep44849
PMID: 28322270
Abstract
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.
Details
- Title: Subtitle
- Huntington’s disease blood and brain show a common gene expression pattern and share an immune signature with Alzheimer’s disease
- Creators
- Davina J Hensman Moss - Department of Neurodegenerative Disease, University College London Institute of NeurologyMichael D Flower - Department of Neurodegenerative Disease, University College London Institute of NeurologyKitty K Lo - University College London Genetics Institute, University College LondonJames R. C Miller - Department of Neurodegenerative Disease, University College London Institute of NeurologyGert-Jan B van Ommen - Department of Human Genetics, Leiden University Medical Center, LeidenPeter A. C ’t Hoen - Department of Human Genetics, Leiden University Medical Center, LeidenTimothy C Stone - MRC Centre for Neuropsychiatric Genetics and Genomics, School of Medicine, Cardiff UniversityAmelia Guinee - Faculty of Education, University of CambridgeDouglas R Langbehn - Departments of Psychiatry and Biostatistics, University of IowaLesley Jones - MRC Centre for Neuropsychiatric Genetics and Genomics, School of Medicine, Cardiff UniversityVincent Plagnol - University College London Genetics Institute, University College LondonWilleke M. C van Roon-Mom - Department of Human Genetics, Leiden University Medical Center, LeidenPeter Holmans - MRC Centre for Neuropsychiatric Genetics and Genomics, School of Medicine, Cardiff UniversitySarah J Tabrizi - Department of Neurodegenerative Disease, University College London Institute of Neurology
- Resource Type
- Journal article
- Publication Details
- Scientific reports, Vol.7(1), pp.44849-44849
- DOI
- 10.1038/srep44849
- PMID
- 28322270
- NLM abbreviation
- Sci Rep
- ISSN
- 2045-2322
- eISSN
- 2045-2322
- Publisher
- Nature Publishing Group
- Language
- English
- Date published
- 03/21/2017
- Academic Unit
- Psychiatry; Iowa Neuroscience Institute
- Record Identifier
- 9984003451802771
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