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Research paper
Platelet abnormalities in Huntington’s disease
  1. Hélèna L Denis1,2,
  2. Jérôme Lamontagne-Proulx1,2,
  3. Isabelle St-Amour1,2,
  4. Sarah L Mason3,
  5. Jesse W Rowley4,
  6. Nathalie Cloutier1,5,
  7. Marie-Ève Tremblay1,6,
  8. Antony T Vincent7,
  9. Peter V Gould8,
  10. Sylvain Chouinard9,
  11. Andrew S Weyrich4,
  12. Matthew T Rondina4,
  13. Roger A Barker3,
  14. Eric Boilard1,5,
  15. Francesca Cicchetti1,2
  1. 1 Centre de Recherche du CHU de Québec, Québec, QC, Canada
  2. 2 Département de Psychiatrie & Neurosciences, Université Laval, Québec, QC, Canada
  3. 3 Department of Clinical Neurosciences, John van Geest Centre for Brain Repair, University of Cambridge, Cambridge, United Kingdom
  4. 4 The Molecular Medicine Program and Department of Internal Medicine, University of Utah The George E. Wahlen VAMC GRECC, Salt Lake City, Utah, USA
  5. 5 Département de microbiologie et immunologie, Faculté de Médecine, Université Laval, Québec, QC, Canada
  6. 6 Département de médecine moléculaire, Faculté de Médecine, Université Laval, Québec, QC, Canada
  7. 7 Département de biochimie, de microbiologie et de bio-informatique, Institut de Biologie Intégrative et des Systèmes, Université Laval, Québec, QC, Canada
  8. 8 Département d'Anatomopathologie et de Cytologie, Centre Hospitalier Affilié Universitaire de Québec, Hôpital de l'Enfant-Jésus, Québec, QC, Canada
  9. 9 Department of Movement Disorders, Centre Hospitalier Universitaire de Montréal-Hôtel Dieu, CHUM, Montréal, QC, Canada
  1. Correspondence to Francesca Cicchetti, Centre de Recherche du CHU de Québec, Département de Psychiatrie & Neurosciences, Université Laval, Québec, QC G1V 4G2, Canada; Francesca.Cicchetti{at}; Eric Boilard, Centre de Recherche du CHU de Québec, Département de microbiologie et immunologie, Faculté de Médecine, Université Laval, Québec, QC, Canada; eric.boilard{at}


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.

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  • EB and FC are joint senior authors.

  • Contributors HLD, JLP and IS-A participated in the design of the experiments and blood drive, data analysis, interpretation and preparations of figures. HLD also helped write the manuscript. IS-A took part in experiments. SLM helped with patient recruitment in Cambridge and participated in the preparation of blood collections in Cambridge. JWR performed RNA-sequencing analysis and helped with interpretations of Figure 2C. NC helped with the RT-qPCR analyses, generated in Figure 2D. MÈT was involved in electron microscopy analysis of Figure 3E. ATV helped with the RNA-sequencing analyses, generated in Figure 2C. PVG helped with all anatomical description provided in Figure 5B. SC recruited patients – Montreal. ASW and MTR were involved in RNA-sequencing analysis and help with interpretations of Figure 2C. RAB recruited patients, participated in data interpretation and revised the manuscript. EB and FC initiated the study and were involved in the experimental design. EB revised the manuscript. FC supervised the project and wrote the manuscript.

  • Funding This study was funded by Fonds de Recherche en Sante du Québec, Santé Merck Sharp and DohmeFondation du CHU de Québec CIHR-Huntington Society of Canada, National Institute for Health Research award of a Biomedical Research Center to the University of Cambridge and Addenbrooke’s Hospital, National Heart, Lung, and Blood Institute and National Institute on Aging (HL112311, HL126547 and AG048022) Centre Thématique de Recherche en Neurosciences du CHU de Québec National Institute for Health Research.

  • Competing interests None declared.

  • Patient consent Not required.

  • Ethics approval CHU de Québec, #A13-02-1096; CHUM, #14.228; Cambridge Central Regional Ethics Committee, REC #03/303 and #08/H0306/26 and Cambridge University Hospitals Foundation Trust Research and Development department, R&D #A085170 and #A091246.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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