Myelin breakdown in human Huntington's disease: Multi-modal evidence from diffusion MRI and quantitative magnetization transfer
Journal article
Bourbon-Teles, José, Bells, Sonya, Jones, Derek K., Coulthard, Elizabeth, Rosser, Anne E. and Metzler-Baddeley, Claudia. (2019). Myelin breakdown in human Huntington's disease: Multi-modal evidence from diffusion MRI and quantitative magnetization transfer. Neuroscience. 403, pp. 79 - 92. https://doi.org/10.1016/j.neuroscience.2017.05.042
Authors | Bourbon-Teles, José, Bells, Sonya, Jones, Derek K., Coulthard, Elizabeth, Rosser, Anne E. and Metzler-Baddeley, Claudia |
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Abstract | Huntington’s disease (HD) leads to white matter (WM) degeneration that may be due to an early breakdown in axon myelination but in vivo imaging correlates of demyelination remain relatively unexplored in HD compared to other neurodegenerative diseases. This study investigated HD-related effects on a putative marker of myelin, the macromolecular proton fraction (MMPF) from quantitative magnetization transfer and on fractional anisotropy, axial and radial diffusivity from diffusion tensor MR-imaging. Microstructural differences were studied in WM pathways of the basal ganglia and motor systems known to be impaired in HD: the corpus callosum, the cortico-spinal tract, the anterior thalamic radiation, fibers between prefrontal cortex and caudate and between supplementary motor area and putamen. Principal component analysis was employed for dimensionality reduction. Patients showed reductions in a component with high loadings on MMPF in all WM pathways and a trend for increases in a component loading on axial and radial diffusivities but no differences in a component loading on fractional anisotropy. While patients’ performance in executive functioning was impaired, their working memory span was preserved. Inter-individual differences in the diffusivity component correlated with patients’ performance in clinical measures of the United Huntington Disease Rating Scale. In summary, HD-related reductions in MMPF suggest that myelin breakdown contributes to WM impairment in human HD and emphasize the potential of quantitative MRI metrics to inform about disease pathogenesis. Disease severity in manifest HD, however, was best captured by non-specific diffusivity metrics sensitive to multiple disease and age-related changes. |
Keywords | Huntington’s disease; myelin; white matter; basal ganglia; cognition; clinical markers |
Year | 2019 |
Journal | Neuroscience |
Journal citation | 403, pp. 79 - 92 |
Publisher | Elsevier Ltd |
ISSN | 0306-4522 |
Digital Object Identifier (DOI) | https://doi.org/10.1016/j.neuroscience.2017.05.042 |
Scopus EID | 2-s2.0-85020896627 |
Open access | Open access |
Page range | 79 - 92 |
Research Group | Mary MacKillop Institute for Health Research |
Publisher's version | License |
Place of publication | United Kingdom |
https://acuresearchbank.acu.edu.au/item/8652z/myelin-breakdown-in-human-huntington-s-disease-multi-modal-evidence-from-diffusion-mri-and-quantitative-magnetization-transfer
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OA_Bourbon_Teles_2019_Myelin_breakdown_in_human_Huntington_s_disease.pdf | |
License: CC BY 4.0 |
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