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Identification of the key role of white matter alteration in the pathogenesis of Huntington’s Disease

Perot, Jean-Baptiste, Celestine, Marina, Palombo, Marco ORCID: https://orcid.org/0000-0003-4892-7967, Dhenain, Marc, Humbert, Sandrine, Brouillet, Emmanuel and Flament, Julien 2021. Identification of the key role of white matter alteration in the pathogenesis of Huntington’s Disease. [Online]. bioRxiv: Cold Spring Harbor Laboratory. Available at: https://doi.org/10.1101/2021.06.21.449242

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Abstract

Pathogenesis of the inherited neurodegenerative disorder Huntington’s Disease (HD) is complex and progressive, with a long presymptomatic phase in which subtle changes occur in the brain of gene carriers up to 15 years before the onset of symptoms. Thus, there is a need of early, functional biomarker to better understand disease progression and to evaluate treatment efficacy far from onset. In particular, recent studies have shown that white matter may be affected early in HD. In this study, we scanned longitudinally Ki140CAG mice with structural MRI, Diffusion Tensor Imaging (DTI), Chemical Exchange Saturation Transfer of glutamate (gluCEST) and Magnetization Transfer (MT) imaging, in order to assess white matter integrity over the life of this very progressive mouse model. Our results show early defects of diffusion properties in the anterior part of the corpus callosum, preceding gluCEST defects in the same region (−10.8% at 8 months, −19% at 12 months) that spread to adjacent regions. At 12 months, frontal (−7.3%) and piriform (−16.7%) cortices showed reduced gluCEST, as well as the pallidum (−21.0%). MT imaging showed reduced signal in the septum (−21.7%) at 12 months. Cortical and striatal atrophy then appear at 18 months. Vulnerability of the striatum and motor cortex, combined with alterations of anterior corpus callosum, seems to point out the pivotal role of white matter, in the pathogenesis of HD and the pertinence of gluCEST and DTI as biomarkers in HD.

Item Type: Website Content
Date Type: Publication
Status: Published
Schools: Psychology
Publisher: Cold Spring Harbor Laboratory
Last Modified: 10 Nov 2022 10:42
URI: https://orca.cardiff.ac.uk/id/eprint/147887

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