PT - JOURNAL ARTICLE AU - Hélèna L Denis AU - Jérôme Lamontagne-Proulx AU - Isabelle St-Amour AU - Sarah L Mason AU - Jesse W Rowley AU - Nathalie Cloutier AU - Marie-Ève Tremblay AU - Antony T Vincent AU - Peter V Gould AU - Sylvain Chouinard AU - Andrew S Weyrich AU - Matthew T Rondina AU - Roger A Barker AU - Eric Boilard AU - Francesca Cicchetti TI - Platelet abnormalities in Huntington’s disease AID - 10.1136/jnnp-2018-318854 DP - 2019 Mar 01 TA - Journal of Neurology, Neurosurgery & Psychiatry PG - 272--283 VI - 90 IP - 3 4099 - http://jnnp.bmj.com/content/90/3/272.short 4100 - http://jnnp.bmj.com/content/90/3/272.full SO - J Neurol Neurosurg Psychiatry2019 Mar 01; 90 AB - Huntington’s 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–brain barrier (BBB) leakage.Objectives 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.Methods 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.Results 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.Conclusion Taken together, our results provide a better understanding for the impact of mHtt on platelet function.