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

Scientific Reports

Volumn 7, Issue , 2017, Pages

  Hensman Moss, Davina J ^a   Flower, Michael D ^a   Lo, Kitty K ^b   Miller, James R C ^a   Van Ommen, Gert Jan B ^c   Hoen, Peter A C T ^c   Stone, Timothy C ^d   Guinee, Amelia ^e   Langbehn, Douglas R ^f   Jones, Lesley ^d   Plagnol, Vincent ^b   Van Roon Mom, Willeke M C ^c   Holmans, Peter ^d   Tabrizi, Sarah J ^a  

^a UNIVERSITY COLLEGE LONDON   (United Kingdom)

^b UNIVERSITY COLLEGE LONDON   (United Kingdom)

^c LEIDEN UNIVERSITY MEDICAL CENTER   (Netherlands)

^d CARDIFF UNIVERSITY   (United Kingdom)

^e UNIVERSITY OF CAMBRIDGE   (United Kingdom)

^f UNIVERSITY OF IOWA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

BIOLOGICAL MARKER; TRANSCRIPTOME;

ADULT; AGED; ALZHEIMER DISEASE; BLOOD; BONE MARROW CELL; BRAIN; CASE CONTROL STUDY; FEMALE; GENE EXPRESSION PROFILING; GENE EXPRESSION REGULATION; GENE REGULATORY NETWORK; GENETICS; HIGH THROUGHPUT SEQUENCING; HUMAN; HUNTINGTON CHOREA; IMMUNITY; IMMUNOLOGY; MALE; METABOLISM; MIDDLE AGED; PREFRONTAL CORTEX; SIGNAL TRANSDUCTION; YOUNG ADULT;

ADULT; AGED; ALZHEIMER DISEASE; BIOMARKERS; BRAIN; CASE-CONTROL STUDIES; FEMALE; GENE EXPRESSION PROFILING; GENE EXPRESSION REGULATION; GENE REGULATORY NETWORKS; HIGH-THROUGHPUT NUCLEOTIDE SEQUENCING; HUMANS; HUNTINGTON DISEASE; IMMUNITY; MALE; MIDDLE AGED; MYELOID CELLS; PREFRONTAL CORTEX; SIGNAL TRANSDUCTION; TRANSCRIPTOME; YOUNG ADULT;

EID: 85015910297     PISSN: None     EISSN: 20452322     Source Type: Journal    
DOI: 10.1038/srep44849     Document Type: Article

References (77)

1. Evans, S. J., et al. Prevalence of adult Huntington's disease in the UK based on diagnoses recorded in general practice records. Journal of neurology, neurosurgery, psychiatry 84, 1156-1160, doi: 10. 1136/jnnp-2012-304636 (2013).
2. Langbehn, D. R., Hayden, M. R., Paulsen, J. S. CAG-repeat length and the age of onset in Huntington disease (HD): a review and validation study of statistical approaches. American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics 153b, 397-408, doi: 10. 1002/ajmg. b. 30992 (2010).
3. Ross, C. A., et al. Huntington disease: natural history, biomarkers and prospects for therapeutics. Nature reviews. Neurology 10, 204-216, doi: 10. 1038/nrneurol. 2014. 24 (2014).
4. Bates, G. P., et al. Huntington disease. Nature Reviews Disease Primers, 15005, doi: 10. 1038/nrdp. 2015. 5 (2015).
5. van der Burg, J. M., Bjorkqvist, M., Brundin, P. Beyond the brain: widespread pathology in Huntington's disease. The Lancet. Neurology 8, 765-774, doi: 10. 1016/S1474-4422(09)70178-4 (2009).
6. Trottier, Y., et al. Cellular localization of the Huntington's disease protein and discrimination of the normal and mutated form. Nature Genetics 10, 104-110, doi: 10. 1038/ng0595-104 (1995).
7. Carroll, J. B., Bates, G. P., Steffan, J., Saft, C., Tabrizi, S. J. Treating the whole body in Huntington's disease. The Lancet. Neurology 14, 1135-1142, doi: 10. 1016/s1474-4422(15)00177-5 (2015).
8. Tai, Y. F., et al. Microglial activation in presymptomatic Huntington's disease gene carriers. Brain 130, 1759-1766, doi: 10. 1093/brain/awm044 (2007).
9. Bjorkqvist, M., et al. A novel pathogenic pathway of immune activation detectable before clinical onset in Huntington's disease. The Journal of experimental medicine 205, 1869-1877, doi: 10. 1084/jem. 20080178 (2008).
10. Kwan, W., et al. Mutant huntingtin impairs immune cell migration in Huntington disease. Journal of Clinical Investigation 122, 4737-4747, doi: 10. 1172/jci64484 (2012).
11. Träger, U., et al. Characterisation of immune cell function in fragment and full-length Huntington's disease mouse models. Neurobiology of disease 73, 388-398, doi: 10. 1016/j. nbd. 2014. 10. 012 (2015).
12. Busse, M. E., Hughes, G., Wiles, C. M., Rosser, A. E. Use of hand-held dynamometry in the evaluation of lower limb muscle strength in people with Huntington's disease. Journal of neurology 255, 1534-1540, doi: 10. 1007/s00415-008-0964-x (2008).
13. Saleh, N., et al. Neuroendocrine disturbances in Huntington's disease. PLoS One 4, e4962, doi: 10. 1371/journal. pone. 0004962 (2009).
14. Lanska, D. J., Lavine, L., Lanska, M. J., Schoenberg, B. S. Huntington's disease mortality in the United States. Neurology 38, 769-772 (1988).
15. Mihm, M. J., et al. Cardiac dysfunction in the R6/2 mouse model of Huntington's disease. Neurobiology of disease 25, 297-308, doi: 10. 1016/j. nbd. 2006. 09. 016 (2007).
16. Pattison, J. S., et al. Cardiomyocyte Expression of a Polyglutamine Preamyloid Oligomer Causes Heart Failure. Circulation 117, 2743-2751, doi: 10. 1161/circulationaha. 107. 750232 (2008).
17. Orth, M., Cooper, J. M., Bates, G. P., Schapira, A. H. V. Inclusion formation in Huntington's disease R6/2 mouse muscle cultures. Journal of Neurochemistry 87, 1-6, doi: 10. 1046/j. 1471-4159. 2003. 02009. x (2003).
18. Turner, C., Cooper, J. M., Schapira, A. H. V. Clinical correlates of mitochondrial function in Huntington's disease muscle. Movement Disorders 22, 1715-1721, doi: 10. 1002/mds. 21540 (2007).
19. Montanini, L., et al. Human RNA integrity after postmortem retinal tissue recovery. Ophthalmic Genet 34, 27-31, doi: 10. 3109/13816810. 2012. 720342 (2013).
20. Tomita, H., et al. Effect of agonal and postmortem factors on gene expression profile: quality control in microarray analyses of postmortem human brain. Biol Psychiatry 55, 346-352, doi: 10. 1016/j. biopsych. 2003. 10. 013 (2004).
21. Hodges, A. Regional and cellular gene expression changes in human Huntington's disease brain. Human molecular genetics 15, 965-977, doi: 10. 1093/hmg/ddl013 (2006).
22. Borovecki, F., et al. Genome-wide expression profiling of human blood reveals biomarkers for Huntington's disease. Proceedings of the National Academy of Sciences of the United States of America 102, 11023-11028, doi: 10. 1073/pnas. 0504921102 (2005).
23. Runne, H., et al. Analysis of potential transcriptomic biomarkers for Huntington's disease in peripheral blood. Proceedings of the National Academy of Sciences of the United States of America 104, 14424-14429, doi: 10. 1073/pnas. 0703652104 (2007).
24. Lovrecic, L., et al. Gene expression changes in blood as a putative biomarker for Huntington's disease. Movement disorders : official journal of the Movement Disorder Society 24, 2277-2281, doi: 10. 1002/mds. 22477 (2009).
25. Mastrokolias, A., et al. Huntington's disease biomarker progression profile identified by transcriptome sequencing in peripheral blood. Eur J Hum Genet, doi: 10. 1038/ejhg. 2014. 281 (2015).
26. Tabrizi, S. J., et al. Biological and clinical manifestations of Huntington's disease in the longitudinal TRACK-HD study: crosssectional analysis of baseline data. The Lancet. Neurology 8, 791-801, doi: 10. 1016/S1474-4422(09)70170-X (2009).
27. Consortium, G. M. o. H. s. D. G.-H. Identification of Genetic Factors that Modify Clinical Onset of Huntington's Disease. Cell 162, 516-526, doi: 10. 1016/j. cell. 2015. 07. 003 (2015).
28. Miller, J. R., et al. RNA-Seq of Huntington's disease patient myeloid cells reveals innate transcriptional dysregulation associated with proinflammatory pathway activation. Human molecular genetics, doi: 10. 1093/hmg/ddw142 (2016).
29. Gibbs, D. L., et al. Protein co-expression network analysis (ProCoNA). Journal of clinical bioinformatics 3, 11, doi: 10. 1186/2043-9113-3-11 (2013).
30. Neueder, A., Bates, G. P. A common gene expression signature in Huntington's disease patient brain regions. BMC medical genomics 7, 60, doi: 10. 1186/s12920-014-0060-2 (2014).
31. Hodges, A., et al. Regional and cellular gene expression changes in human Huntington's disease brain. Human molecular genetics 15, 965-977, doi: 10. 1093/hmg/ddl013 (2006).
32. Braineac. Braineac-The Brain eQTL Almanac, http://www. braineac. org/(2016).
33. Gibbs, J. R., et al. Abundant quantitative trait loci exist for DNA methylation and gene expression in human brain. PLoS genetics 6, e1000952, doi: 10. 1371/journal. pgen. 1000952 (2010).
34. Langfelder, P., Horvath, S. WGCNA: an R package for weighted correlation network analysis. BMC bioinformatics 9, 559, doi: 10. 1186/1471-2105-9-559 (2008).
35. Labadorf, A., et al. RNA Sequence Analysis of Human Huntington Disease Brain Reveals an Extensive Increase in Inflammatory and Developmental Gene Expression. PLOS ONE 10, e0143563, doi: 10. 1371/journal. pone. 0143563 (2015).
36. Gomez-Nicola, D., Fransen, N. L., Suzzi, S., Perry, V. H. Regulation of microglial proliferation during chronic neurodegeneration. The Journal of neuroscience : the official journal of the Society for Neuroscience 33, 2481-2493, doi: 10. 1523/JNEUROSCI. 4440-12. 2013 (2013).
37. Olmos-Alonso, A., et al. Pharmacological targeting of CSF1R inhibits microglial proliferation and prevents the progression of Alzheimer's-like pathology. Brain 139, 891-907, doi: 10. 1093/brain/awv379 (2016).
38. Hong, S., et al. Complement and microglia mediate early synapse loss in Alzheimer mouse models. Science (New York, N. Y. ), doi: 10. 1126/science. aad8373 (2016).
39. International Genomics of Alzheimer's Disease, C. Convergent genetic and expression data implicate immunity in Alzheimer's disease. Alzheimers Dement 11, 658-671, doi: 10. 1016/j. jalz. 2014. 05. 1757 (2015).
40. Zhang, B., et al. Integrated systems approach identifies genetic nodes and networks in late-onset Alzheimer's disease. Cell 153, 707-720, doi: 10. 1016/j. cell. 2013. 03. 030 (2013).
41. Costa, V., Angelini, C., De Feis, I., Ciccodicola, A. Uncovering the complexity of transcriptomes with RNA-Seq. Journal of biomedicine & biotechnology 2010, 853916, doi: 10. 1155/2010/853916 (2010).
42. Kegel-Gleason, K. B. Huntingtin interactions with membrane phospholipids: strategic targets for therapeutic intervention? Journal of Huntington's disease 2, 239-250, doi: 10. 3233/JHD-130068 (2013).
43. Wild, E., et al. Abnormal peripheral chemokine profile in Huntington's disease. PLoS currents 3, RRN1231, doi: 10. 1371/currents. rrn1231 (2011).
44. Whitney, A. R., et al. Individuality and variation in gene expression patterns in human blood. Proceedings of the National Academy of Sciences of the United States of America 100, 1896-1901, doi: 10. 1073/pnas. 252784499 (2003).
45. Horvath, S., et al. Aging effects on DNA methylation modules in human brain and blood tissue. Genome Biol 13, R97, doi: 10. 1186/gb-2012-13-10-r97 (2012).
46. Cai, C., et al. Is human blood a good surrogate for brain tissue in transcriptional studies? BMC genomics 11, 589, doi: 10. 1186/1471-2164-11-589 (2010).
47. Bouchard, J., et al. Cannabinoid Receptor 2 Signaling in Peripheral Immune Cells Modulates Disease Onset and Severity in Mouse Models of Huntington's Disease. Journal of Neuroscience 32, 18259-18268, doi: 10. 1523/jneurosci. 4008-12. 2012 (2012).
48. Kwan, W., et al. Bone Marrow Transplantation Confers Modest Benefits in Mouse Models of Huntington's Disease. Journal of Neuroscience 32, 133-142, doi: 10. 1523/jneurosci. 4846-11. 2012 (2012).
49. Seredenina, T., Luthi-Carter, R. What have we learned from gene expression profiles in Huntington's disease? Neurobiology of disease 45, 83-98, doi: 10. 1016/j. nbd. 2011. 07. 001 (2012).
50. Mochel, F., et al. Early alterations of brain cellular energy homeostasis in Huntington disease models. The Journal of biological chemistry 287, 1361-1370, doi: 10. 1074/jbc. M111. 309849 (2012).
51. Seong, I. S. HD CAG repeat implicates a dominant property of huntingtin in mitochondrial energy metabolism. Human molecular genetics 14, 2871-2880, doi: 10. 1093/hmg/ddi319 (2005).
52. Cui, L., et al. Transcriptional repression of PGC-1alpha by mutant huntingtin leads to mitochondrial dysfunction and neurodegeneration. Cell 127, 59-69, doi: 10. 1016/j. cell. 2006. 09. 015 (2006).
53. Chaturvedi, R. K., et al. Impairment of PGC-1alpha expression, neuropathology and hepatic steatosis in a transgenic mouse model of Huntington's disease following chronic energy deprivation. Human molecular genetics 19, 3190-3205, doi: 10. 1093/hmg/ddq229 (2010).
54. Jonson, I., Ougland, R., Larsen, E. DNA repair mechanisms in Huntington's disease. Molecular neurobiology 47, 1093-1102, doi: 10. 1007/s12035-013-8409-7 (2013).
55. Morton, A. J., Howland, D. S. Large genetic animal models of Huntington's Disease. Journal of Huntington's disease 2, 3-19, doi: 10. 3233/jhd-130050 (2013).
56. Ehrnhoefer, D. E., Butland, S. L., Pouladi, M. A., Hayden, M. R. Mouse models of Huntington disease: variations on a theme. Disease Models & Mechanisms 2, 123-129, doi: 10. 1242/dmm. 002451 (2009).
57. Mina, E., et al. Common disease signatures between blood and brain in Huntington's Disease. Orphanet Journal of Rare Diseases (2016).
58. Wyss-Coray, T., Rogers, J. Inflammation in Alzheimer disease-a brief review of the basic science and clinical literature. Cold Spring Harb Perspect Med 2, a006346, doi: 10. 1101/cshperspect. a006346 (2012).
59. Hong, S., Dissing-Olesen, L., Stevens, B. New insights on the role of microglia in synaptic pruning in health and disease. Curr Opin Neurobiol 36, 128-134, doi: 10. 1016/j. conb. 2015. 12. 004 (2016).
60. Penney, J. B. Jr., Vonsattel, J. P., MacDonald, M. E., Gusella, J. F., Myers, R. H. CAG repeat number governs the development rate of pathology in Huntington's disease. Ann Neurol 41, 689-692, doi: 10. 1002/ana. 410410521 (1997).
61. Group, H. S. Unified Huntington's Disease Rating Scale: reliability and consistency. Huntington Study Group. Movement disorders : official journal of the Movement Disorder Society 11, 136-142, doi: 10. 1002/mds. 870110204 (1996).
62. Illumina. TruSeq(R) RNA Sample Preparation v2 Guide, http://support. illumina. com/content/dam/illumina-support/documents/documentation/chemistry-documentation/samplepreps-truseq/truseqrna/truseq-rna-sample-prep-v2-guide-15026495-f. pdf (2014).
63. DeLuca, D. S., et al. RNA-SeQC: RNA-seq metrics for quality control and process optimization. Bioinformatics 28, 1530-1532, doi: 10. 1093/bioinformatics/bts196 (2012).
64. Kim, D., et al. TopHat2: accurate alignment of transcriptomes in the presence of insertions, deletions and gene fusions. Genome Biol 14, R36, doi: 10. 1186/gb-2013-14-4-r36 (2013).
65. Leek, J. T. svaseq: removing batch effects and other unwanted noise from sequencing data. Nucleic Acids Res 42, doi: 10. 1093/nar/gku864 (2014).
66. Love, M. I., Huber, W., Anders, S. Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol 15, 550, doi: 10. 1186/s13059-014-0550-8 (2014).
67. Subramanian, A., et al. Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. Proceedings of the National Academy of Sciences of the United States of America 102, 15545-15550, doi: 10. 1073/pnas. 0506580102 (2005).
68. Consortium, G. O. Gene Ontology Consortium, http://geneontology. org/(2016).
69. KEGG. KEGG: Kyoto Encyclopedia of Genes and Genomes, http://www. kegg. jp/(2016).
70. MGI. MGI-Mouse Genome Informatics-The international database resource for the laboratory mouse, http://www. informatics. jax. org/(2016).
71. PANTHER. PANTHER-Gene List Analysis, http://pantherdb. org/(2016).
72. BioCarta. http://www. biocarta. com/. (2016).
73. REACTOME. Reactome Pathway Database, http://www. reactome. org/(2016).
74. Institute, N. C. Home : Pathway Interaction Database, http://www. ncbi. nlm. nih. gov/pubmed/(2012).
75. Storey, J. D., Tibshirani, R. Statistical significance for genomewide studies. Proceedings of the National Academy of Sciences of the United States of America 100, 9440-9445, doi: 10. 1073/pnas. 1530509100 (2003).
76. Carvalho, B. S., Irizarry, R. A. A framework for oligonucleotide microarray preprocessing. Bioinformatics 26, 2363-2367, doi: 10. 1093/bioinformatics/btq431 (2010).
77. Affymetrix. Affymetrix, http://www. affymetrix. com/estore/index. jsp (2016).