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Myelin Breakdown in Human Huntington’s Disease: Multi-Modal Evidence from Diffusion MRI and Quantitative Magnetization Transfer
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...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier Science
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6458992/ https://www.ncbi.nlm.nih.gov/pubmed/28579146 http://dx.doi.org/10.1016/j.neuroscience.2017.05.042 |
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author | Bourbon-Teles, José Bells, Sonya Jones, Derek K. Coulthard, Elizabeth Rosser, Anne Metzler-Baddeley, Claudia |
author_facet | Bourbon-Teles, José Bells, Sonya Jones, Derek K. Coulthard, Elizabeth Rosser, Anne Metzler-Baddeley, Claudia |
author_sort | Bourbon-Teles, José |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-6458992 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Elsevier Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-64589922019-04-22 Myelin Breakdown in Human Huntington’s Disease: Multi-Modal Evidence from Diffusion MRI and Quantitative Magnetization Transfer Bourbon-Teles, José Bells, Sonya Jones, Derek K. Coulthard, Elizabeth Rosser, Anne Metzler-Baddeley, Claudia Neuroscience Article 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. Elsevier Science 2019-04-01 /pmc/articles/PMC6458992/ /pubmed/28579146 http://dx.doi.org/10.1016/j.neuroscience.2017.05.042 Text en © 2017 The Author(s) http://creativecommons.org/licenses/by/4.0/ This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Bourbon-Teles, José Bells, Sonya Jones, Derek K. Coulthard, Elizabeth Rosser, Anne Metzler-Baddeley, Claudia Myelin Breakdown in Human Huntington’s Disease: Multi-Modal Evidence from Diffusion MRI and Quantitative Magnetization Transfer |
title | Myelin Breakdown in Human Huntington’s Disease: Multi-Modal Evidence from Diffusion MRI and Quantitative Magnetization Transfer |
title_full | Myelin Breakdown in Human Huntington’s Disease: Multi-Modal Evidence from Diffusion MRI and Quantitative Magnetization Transfer |
title_fullStr | Myelin Breakdown in Human Huntington’s Disease: Multi-Modal Evidence from Diffusion MRI and Quantitative Magnetization Transfer |
title_full_unstemmed | Myelin Breakdown in Human Huntington’s Disease: Multi-Modal Evidence from Diffusion MRI and Quantitative Magnetization Transfer |
title_short | Myelin Breakdown in Human Huntington’s Disease: Multi-Modal Evidence from Diffusion MRI and Quantitative Magnetization Transfer |
title_sort | myelin breakdown in human huntington’s disease: multi-modal evidence from diffusion mri and quantitative magnetization transfer |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6458992/ https://www.ncbi.nlm.nih.gov/pubmed/28579146 http://dx.doi.org/10.1016/j.neuroscience.2017.05.042 |
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