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12.09.2018 | Original Communication | Ausgabe 11/2018

Journal of Neurology 11/2018

Platelet-derived extracellular vesicles in Huntington’s disease

Zeitschrift:
Journal of Neurology > Ausgabe 11/2018
Autoren:
Hélèna L. Denis, Jérôme Lamontagne-Proulx, Isabelle St-Amour, Sarah L. Mason, Andreas Weiss, Sylvain Chouinard, Roger A. Barker, Eric Boilard, Francesca Cicchetti
Wichtige Hinweise

Electronic supplementary material

The online version of this article (https://​doi.​org/​10.​1007/​s00415-018-9022-5) contains supplementary material, which is available to authorized users.
Hélèna L. Denis and Jérôme Lamontagne-Proulx contributed equally to this work.

Abstract

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.

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Zusatzmaterial
Supplementary material 1 Figure S1. Identified biomarkers in HD. Summary of the literature for all reported biomarkers of HD in CSF, blood, urine and brain. Abbreviations: DOPA: 3,4-dihydroxyphenylalanine; DOPAC: 3,4-dihydroxyphenylacetic acid; IL-6: Interleukin 6;IL-8: Interleukin 8; NMDA: N-methyl-D-aspartate; mHtt: mutant huntingtin; Cu/Zn-SOD: Cu/Zn Superoxide Dismutase; HD: Huntington disease; PCYT1A: Phosphate Cytidylyltransferase 1, Pre-HD : pre-manifest, Choline, Alpha; YKL-40: chitinase-like protein-40; 5-HIAA: 5-hydroxyindoleacetic acid; 8-OHdG: 8-hydroxy-2’ -deoxyguanosine; 8-oxodG6: 8-oxo-7,8-dihydro-2′-deoxyguanosine; ↑ ; increase; ↓; decrease; ✔; presence (PDF 13620 KB)
415_2018_9022_MOESM1_ESM.pdf
Supplementary material 2 Figure S2. (A) Absence of statistical differences in comorbidities of healthy control patients - which including depression (p=0.2455), diabetes (p=0.0749), hypertension (p=0.9664), hypercholesterolemia (p=0.3615), allergies (p=0.9904) and anxiety (p=0.4675) - and counts of EV derived from platelets. EV from patients without comorbidities were further compared to patients with one or more comorbidities. Again, no statistically significant differences were found (p=0.6745). Statistical analyses were performed using the non-parametric Mann Whitney test. (B) Immunoblot of CD41a, ALIX, TSG101, actin and VDAC in platelet-derived EV or plts. Data are representative of 3 independent experiments. (C) Left panel: After the acquisition of fluorescent signals, an initial gating was performed on all data to exclude counting beads from files. In this experiment, 144 beads were counted. Right panel: Representation of SSC-H (granularity) and FSC-PMT-H (relative size) dot plots of platelet-derived EV in PFP detecting using PerCP-CyTM5.5-conjugated annexin V and V450-conjugated antibodies directed against CD41. The size of platelet-derived EV ranged between 100 and 1000nm. Abbreviations: ALIX, programmed cell death 6 interacting protein; EV, extracellular vesicles; plts, platelets; TSG101, tumor susceptibility gene 101 protein; VDAC, Voltage-dependent anion-selective channel 1 (PDF 1813 KB)
415_2018_9022_MOESM2_ESM.pdf
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