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Characterising white matter in Huntington's disease

Gregory, S; Johnson, E; Byrne, L; Rodrigues, F; Henderson, A; Moss, J; Thomas, D; ... Wild, E; + view all (2020) Characterising white matter in Huntington's disease. Movement Disorders Clinical Practice , 7 (1) pp. 52-60. 10.1002/mdc3.12866. Green open access

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Abstract

Background: Investigating early white matter (WM) change in Huntington’s Disease (HD) can improve our understanding of the way in which disease spreads from the striatum. Objectives: Here, we provide a detailed characterisation of pathology-related WM change in HD. We first examined WM microstructure using diffusion-weighted imaging, then investigated both underlying biological properties of WM and products of WM damage including iron, myelin plus neurofilament light (NfL), a biofluid marker of axonal degeneration – in parallel with the mutant huntingtin protein (mHTT). Methods: We examined WM change in HD gene-carriers from the HD-CSF cohort, baseline visit. We used standard diffusion MRI to measure metrics including fractional anisotropy (FA), a marker of WM integrity, and diffusivity; a novel diffusion model (NODDI) to measure axonal density and organisation; T1 and T2 weighted structural MRI images to derive proxy iron content and myelin-contrast measures; and biofluid concentrations of NfL (in CSF and plasma) and mHTT (in CSF). Results: HD gene-carriers displayed reduced FA and increased diffusivity compared to controls, both of which were also associated with disease progression, CSF and mHTT levels. HD gene-carriers also displayed proxy measures of reduced myelin-contrast and iron in the striatum. Conclusion: Collectively, these findings present a more complete characterisation of HD-related microstructural brain changes. Correlation between reduced FA, increased axonal orientation and biofluid markers suggest that axonal breakdown is associated with increased WM degeneration, while higher quantitative T2 signal and lower myelin-contrast may indicate a process of demyelination limited to the striatum.

Type: Article
Title: Characterising white matter in Huntington's disease
Open access status: An open access version is available from UCL Discovery
DOI: 10.1002/mdc3.12866
Publisher version: https://doi.org/10.1002/mdc3.12866
Language: English
Additional information: © 2019 University College London. Movement Disorders Clinical Practice published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Brain Repair and Rehabilitation
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Neurodegenerative Diseases
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > UCL BEAMS
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science > Dept of Computer Science
URI: https://discovery.ucl.ac.uk/id/eprint/10084644
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