{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T00:38:52Z","timestamp":1793320732271,"version":"4.5.0"},"reference-count":48,"publisher":"BMJ","issue":"3","funder":[{"DOI":"10.13039\/501100000156","name":"Fonds de Recherche du Qu\u00e9bec - Sant\u00e9","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000156","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009947","name":"Merck Sharp and Dohme","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100009947","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004889","name":"Fondation du CHU de Qu\u00e9bec","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100004889","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100009836","name":"Huntington Society of Canada","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100009836","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Centre Th\u00e9matique de Recherche en Neurosciences du CHU de Qu\u00e9bec"},{"DOI":"10.13039\/501100000272","name":"National Institute for Health Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000272","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Neurol Neurosurg Psychiatry"],"published-print":{"date-parts":[[2019,3]]},"abstract":"<jats:p>Huntington\u2019s disease (HD) is a hereditary disorder that typically manifests in adulthood with a combination of motor, cognitive and psychiatric problems. The pathology is caused by a mutation in the huntingtin gene which results in the production of an abnormal protein, mutant huntingtin (mHtt). This protein is ubiquitously expressed and known to confer toxicity to multiple cell types. We have recently reported that HD brains are also characterised by vascular abnormalities, which include changes in blood vessel density\/diameter as well as increased blood\u2013brain barrier (BBB) leakage.<\/jats:p><jats:sec><jats:title>Objectives<\/jats:title><jats:p>Seeking to elucidate the origin of these vascular and BBB abnormalities, we studied platelets that are known to play a role in maintaining the integrity of the vasculature and thrombotic pathways linked to this, given they surprisingly contain the highest concentration of mHtt of all blood cells.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We assessed the functional status of platelets by performing ELISA, western blot and RNA sequencing in a cohort of 71 patients and 68 age- and sex-matched healthy control subjects. We further performed haemostasis and platelet depletion tests in the R6\/2 HD mouse model.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Our findings indicate that the platelets in HD are dysfunctional with respect to the release of angiogenic factors and functions including thrombosis, angiogenesis and vascular haemostasis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Taken together, our results provide a better understanding for the impact of mHtt on platelet function.<\/jats:p><\/jats:sec>","DOI":"10.1136\/jnnp-2018-318854","type":"journal-article","created":{"date-parts":[[2018,12,19]],"date-time":"2018-12-19T22:19:29Z","timestamp":1545257969000},"page":"272-283","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":45,"title":["Platelet abnormalities in Huntington\u2019s disease"],"prefix":"10.1136","volume":"90","author":[{"given":"H\u00e9l\u00e8na L","family":"Denis","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00e9r\u00f4me","family":"Lamontagne-Proulx","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabelle","family":"St-Amour","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah L","family":"Mason","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jesse W","family":"Rowley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathalie","family":"Cloutier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie-\u00c8ve","family":"Tremblay","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antony T","family":"Vincent","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter V","family":"Gould","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sylvain","family":"Chouinard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew S","family":"Weyrich","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew T","family":"Rondina","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roger A","family":"Barker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Boilard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Cicchetti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2018,12,19]]},"reference":[{"key":"2023072002302165000_90.3.272.1","doi-asserted-by":"crossref","unstructured":"Bates GP , Dorsey R , Gusella JF . Huntington disease. Nat Rev Dis Primer 2015;1:nrdp20155.","DOI":"10.1038\/nrdp.2015.5"},{"key":"2023072002302165000_90.3.272.2","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2009.05.012"},{"key":"2023072002302165000_90.3.272.3","doi-asserted-by":"publisher","DOI":"10.1172\/JCI64565"},{"key":"2023072002302165000_90.3.272.4","doi-asserted-by":"publisher","DOI":"10.1002\/ana.24406"},{"key":"2023072002302165000_90.3.272.5","doi-asserted-by":"publisher","DOI":"10.1002\/ana.24428"},{"key":"2023072002302165000_90.3.272.6","doi-asserted-by":"crossref","unstructured":"Di Pardo A , Amico E , Scalabr\u00ec F , et al . Impairment of blood-brain barrier is an early event in R6\/2 mouse model of Huntington Disease. Sci Rep 2017;7:41316.doi:10.1038\/srep41316","DOI":"10.1038\/srep41316"},{"key":"2023072002302165000_90.3.272.7","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1038\/nrrheum.2018.38","article-title":"The non-haemostatic role of platelets in systemic lupus erythematosus","volume":"14","author":"Linge","year":"2018","journal-title":"Nat Rev Rheumatol"},{"key":"2023072002302165000_90.3.272.8","doi-asserted-by":"publisher","DOI":"10.3109\/00207454.2012.751534"},{"key":"2023072002302165000_90.3.272.9","doi-asserted-by":"publisher","DOI":"10.1097\/BOT.0b013e31817e793f"},{"key":"2023072002302165000_90.3.272.10","doi-asserted-by":"publisher","DOI":"10.1111\/j.1538-7836.2011.04317.x"},{"key":"2023072002302165000_90.3.272.11","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.114.301611"},{"key":"2023072002302165000_90.3.272.12","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2012-02-413047"},{"key":"2023072002302165000_90.3.272.13","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1007\/s10555-017-9673-1","article-title":"Platelets and cancer angiogenesis nexus","volume":"36","author":"Wojtukiewicz","year":"2017","journal-title":"Cancer Metastasis Rev"},{"key":"2023072002302165000_90.3.272.14","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0702191"},{"key":"2023072002302165000_90.3.272.15","doi-asserted-by":"publisher","DOI":"10.1016\/S0049-3848(03)00142-7"},{"key":"2023072002302165000_90.3.272.16","first-page":"523","article-title":"Angiogenic factors are hematopoietic growth factors and vice versa","volume":"8","author":"Bikfalvi","year":"1994","journal-title":"Leukemia"},{"key":"2023072002302165000_90.3.272.17","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-08-0718"},{"key":"2023072002302165000_90.3.272.18","doi-asserted-by":"crossref","unstructured":"Lamontagne-Proulx J , St-Amour I , Labib R , et al . Portrait of blood-derived extracellular vesicles in patients with Parkinson\u2019s disease. Neurobiol Dis (In revision) 2018.","DOI":"10.1016\/j.nbd.2018.11.002"},{"key":"2023072002302165000_90.3.272.19","doi-asserted-by":"crossref","unstructured":"Denis HL , Lamontagne-Proulx J , St-Amour I . Platelet-derived extracellular vesicles in Huntington\u2019s disease. J Neurol 2018;10.doi:10.1007\/s00415-018-9022-5","DOI":"10.1007\/s00415-018-9022-5"},{"key":"2023072002302165000_90.3.272.20","doi-asserted-by":"publisher","DOI":"10.1111\/j.1538-7836.2011.04610.x"},{"key":"2023072002302165000_90.3.272.21","doi-asserted-by":"crossref","unstructured":"Nix DA , Courdy SJ , Boucher KM . Empirical methods for controlling false positives and estimating confidence in ChIP-Seq peaks. BMC Bioinformatics 2008;9:523.doi:10.1186\/1471-2105-9-523","DOI":"10.1186\/1471-2105-9-523"},{"key":"2023072002302165000_90.3.272.22","doi-asserted-by":"crossref","unstructured":"Love MI , Huber W , Anders S . Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol 2014;15:550.doi:10.1186\/s13059-014-0550-8","DOI":"10.1186\/s13059-014-0550-8"},{"key":"2023072002302165000_90.3.272.23","unstructured":"R Core Team , 2016. R: a language and environment for statistical computing. Available from: https:\/\/www.R-project.org\/"},{"key":"2023072002302165000_90.3.272.24","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btl117"},{"key":"2023072002302165000_90.3.272.25","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2011-03-339705"},{"key":"2023072002302165000_90.3.272.26","doi-asserted-by":"publisher","DOI":"10.1373\/clinchem.2008.112797"},{"key":"2023072002302165000_90.3.272.27","doi-asserted-by":"publisher","DOI":"10.1006\/meth.2001.1262"},{"key":"2023072002302165000_90.3.272.28","doi-asserted-by":"crossref","unstructured":"Tremblay ME , Riad M , Majewska A . Preparation of mouse brain tissue for immunoelectron microscopy. J Vis Exp 2010;2021.doi:10.3791\/2021","DOI":"10.3791\/2021"},{"key":"2023072002302165000_90.3.272.29","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)63824-2"},{"key":"2023072002302165000_90.3.272.30","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2005.09.037"},{"key":"2023072002302165000_90.3.272.31","first-page":"116","article-title":"Uptake of 5-hydroxytryptamine by blood platelets in Huntington's chorea and Alzheimer type of presenile dementia","volume":"59","author":"Tukiainen","year":"1981","journal-title":"Med Biol"},{"key":"2023072002302165000_90.3.272.32","doi-asserted-by":"crossref","first-page":"1115","DOI":"10.1016\/S0140-6736(74)90873-3","article-title":"Plasma uptake of dopamine and 5-hydroxytryptamine and plasma-catecholamine levels in patients with Huntington's chorea","volume":"2","author":"Aminoff","year":"1974","journal-title":"Lancet"},{"key":"2023072002302165000_90.3.272.33","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1016\/0022-510X(94)90134-1","article-title":"Huntington's disease: the neuroexcitotoxin aspartate is increased in platelets and decreased in plasma","volume":"127","author":"Reilmann","year":"1994","journal-title":"J Neurol Sci"},{"key":"2023072002302165000_90.3.272.34","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410390317"},{"key":"2023072002302165000_90.3.272.35","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1016\/0364-7722(80)90048-X","article-title":"Platelet aggregation, 5-hydroxytryptamine uptake and release in Huntington's chorea","volume":"4","author":"Diez-Ewald","year":"1980","journal-title":"Prog Neuropsychopharmacol"},{"key":"2023072002302165000_90.3.272.36","doi-asserted-by":"crossref","unstructured":"del Rey M , Benito R , Fontanillo C , et al . Deregulation of genes related to iron and mitochondrial metabolism in refractory anemia with ring sideroblasts. PLoS One 2015;10:e0126555.doi:10.1371\/journal.pone.0126555","DOI":"10.1371\/journal.pone.0126555"},{"key":"2023072002302165000_90.3.272.37","doi-asserted-by":"publisher","DOI":"10.1016\/j.mito.2013.05.006"},{"key":"2023072002302165000_90.3.272.38","doi-asserted-by":"publisher","DOI":"10.1111\/j.1742-4658.2006.05537.x"},{"key":"2023072002302165000_90.3.272.39","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2011-12-396440"},{"key":"2023072002302165000_90.3.272.40","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.1RU0916-391RR"},{"key":"2023072002302165000_90.3.272.41","doi-asserted-by":"crossref","first-page":"3037","DOI":"10.1182\/blood.V94.9.3037","article-title":"Pathophysiology of thrombocytopenia and anemia in mice lacking transcription factor NF-E2","volume":"94","author":"Levin","year":"1999","journal-title":"Blood"},{"key":"2023072002302165000_90.3.272.42","doi-asserted-by":"crossref","unstructured":"Close J , Game L , Clark B , et al . Genome annotation of a 1.5 Mb region of human chromosome 6q23 encompassing a quantitative trait locus for fetal hemoglobin expression in adults. BMC Genomics 2004;5:33.doi:10.1186\/1471-2164-5-33","DOI":"10.1186\/1471-2164-5-33"},{"key":"2023072002302165000_90.3.272.43","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-005-5084-5"},{"key":"2023072002302165000_90.3.272.44","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.119.3.629"},{"key":"2023072002302165000_90.3.272.45","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1007\/s11010-015-2545-5","article-title":"The role of FGF2 in migration and tubulogenesis of endothelial progenitor cells in relation to pro-angiogenic growth factor production","volume":"410","author":"Litwin","year":"2015","journal-title":"Mol Cell Biochem"},{"key":"2023072002302165000_90.3.272.46","doi-asserted-by":"crossref","unstructured":"Herr N , Bode C , Duerschmied D . The effects of serotonin in immune cells. Front Cardiovasc Med 2017;4:48.doi:10.3389\/fcvm.2017.00048","DOI":"10.3389\/fcvm.2017.00048"},{"key":"2023072002302165000_90.3.272.47","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1007\/BF02141780","article-title":"Abnormal platelet aggregation response in Huntington's disease","volume":"232","author":"Muramatsu","year":"1982","journal-title":"Arch Psychiatr Nervenkr"},{"key":"2023072002302165000_90.3.272.48","doi-asserted-by":"crossref","first-page":"56","DOI":"10.2478\/s13380-012-0001-5","article-title":"Antipsychotics do not affect platelet serotonin in schizophrenic patients","volume":"3","author":"Sagud","year":"2012","journal-title":"Transl Neurosci"}],"updated-by":[{"DOI":"10.1136\/jnnp-2018-318854corr1","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2019,6,13]],"date-time":"2019-06-13T00:00:00Z","timestamp":1560384000000}}],"container-title":["Journal of Neurology, Neurosurgery &amp; Psychiatry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/jnnp-2018-318854","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,7,20]],"date-time":"2023-07-20T09:40:28Z","timestamp":1689846028000},"score":1,"resource":{"primary":{"URL":"https:\/\/jnnp.bmj.com\/lookup\/doi\/10.1136\/jnnp-2018-318854"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,12,19]]},"references-count":48,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2019,2,14]]},"published-print":{"date-parts":[[2019,3]]}},"alternative-id":["10.1136\/jnnp-2018-318854"],"URL":"https:\/\/doi.org\/10.1136\/jnnp-2018-318854","relation":{"correction":[{"id-type":"doi","id":"10.1136\/jnnp-2018-318854corr1","asserted-by":"object"}]},"ISSN":["0022-3050","1468-330X"],"issn-type":[{"value":"0022-3050","type":"print"},{"value":"1468-330X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,12,19]]}}}