Platelet-derived extracellular vesicles in Huntington's disease.
Denis, Hélèna L
Mason, Sarah L
Barker, Roger A
Springer Science and Business Media LLC
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Denis, H. L., Lamontagne-Proulx, J., St-Amour, I., Mason, S. L., Weiss, A., Chouinard, S., Barker, R. A., et al. (2018). Platelet-derived extracellular vesicles in Huntington's disease.. J Neurol, 265 (11), 2704-2712. https://doi.org/10.1007/s00415-018-9022-5
The production and release of extracellular vesicles (EV) is a property shared by all eukaryotic cells and a phenomenon frequently exacerbated in pathological conditions. The protein cargo of EV, their cell type signature and availability in bodily fluids make them particularly appealing as biomarkers. We recently demonstrated that platelets, among all types of blood cells, contain the highest concentrations of the mutant huntingtin protein (mHtt)-the genetic product of Huntington's disease (HD), a neurodegenerative disorder which manifests in adulthood with a complex combination of motor, cognitive and psychiatric deficits. Herein, we used a cohort of 59 HD patients at all stages of the disease, including individuals in pre-manifest stages, and 54 healthy age- and sex-matched controls, to evaluate the potential of EV derived from platelets as a biomarker. We found that platelets of pre-manifest and manifest HD patients do not release more EV even if they are activated. Importantly, mHtt was not found within EV derived from platelets, despite them containing high levels of this protein. Correlation analyses also failed to reveal an association between the number of platelet-derived EV and the age of the patients, the number of CAG repeats, the Unified Huntington Disease Rating Scale total motor score, the Total Functional Capacity score or the Burden of Disease score. Our data would, therefore, suggest that EV derived from platelets with HD is not a valuable biomarker in HD.
Blood Platelets, Humans, Huntington Disease, Adult, Aged, Middle Aged, Female, Male, Biomarkers, Extracellular Vesicles, Huntingtin Protein
The study was funded by an operating grant from the Merck Sharpe & Dohme to F.C. who is also a recipient of a National Researcher career award from the Fonds de Recherche du Québec en santé (FRQS) providing salary support and operating funds. I.S.-A. was supported by a CIHR-Huntington Society of Canada postdoctoral fellowship. R.A.B. and S.L.M. are supported by a National Institute for Health Research (NIHR) award of a Biomedical Research Center to the University of Cambridge and Addenbrooke’s Hospital. E.B. is supported by the Canadian Institutes of Health Research. N.D. MD-MSc. also funded by CIHR and by Canadian Consortium on Neurodegeneration in Aging (CCNA). HLD and JPL hold a Desjardins scholarship from the Fondation du CHU de Québec. HLD hold a bourse d’excellence du Centre Thématique de Recherche en Neurosciences (CTRN) du CHU de Québec. The authors would like to thank all the students and staff who helped with the blood collections in Cambridge, Quebec City and Montreal and importantly, all patients and their families for being so generous with their time in participating to this study
External DOI: https://doi.org/10.1007/s00415-018-9022-5
This record's URL: https://www.repository.cam.ac.uk/handle/1810/284975