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Cortical neurodevelopment in pre-manifest Huntington's disease
BACKGROUND: The expression of the HTT CAG repeat expansion mutation causes neurodegeneration in Huntington's disease (HD). Objectives: In light of the – mainly in-vitro – evidence suggesting an additional role of huntingtin in neurodevelopment we used 3T MRI to test the hypothesis that in CAG-e...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6627026/ https://www.ncbi.nlm.nih.gov/pubmed/31491822 http://dx.doi.org/10.1016/j.nicl.2019.101913 |
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author | Kubera, Katharina M. Schmitgen, Mike M. Hirjak, Dusan Wolf, Robert Christian Orth, Michael |
author_facet | Kubera, Katharina M. Schmitgen, Mike M. Hirjak, Dusan Wolf, Robert Christian Orth, Michael |
author_sort | Kubera, Katharina M. |
collection | PubMed |
description | BACKGROUND: The expression of the HTT CAG repeat expansion mutation causes neurodegeneration in Huntington's disease (HD). Objectives: In light of the – mainly in-vitro – evidence suggesting an additional role of huntingtin in neurodevelopment we used 3T MRI to test the hypothesis that in CAG-expanded individuals without clinical signs of HD (preHD) there is evidence for neurodevelopmental abnormalities. METHODS: We specifically investigated the complexity of cortical folding, a measure of cortical neurodevelopment, employing a novel method to quantify local fractal dimension (FD) measures that uses spherical harmonic reconstructions. RESULTS: The complexity of cortical folding differed at a group level between preHD (n = 57) and healthy volunteers (n = 57) in areas of the motor and visual system as well as temporal cortical areas. However, there was no association between the complexity of cortical folding and the loss in putamen volume that was clearly evident in preHD. CONCLUSIONS: Our results suggest that HTT CAG repeat length may have an influence on cortical folding without evidence that this leads to developmental pathology or was clinically meaningful. This suggests that the HTT CAG-repeat expansion mutation may influence the processes governing cortical neurodevelopment; however, that influence seems independent of the events that lead to neurodegeneration. |
format | Online Article Text |
id | pubmed-6627026 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-66270262019-07-23 Cortical neurodevelopment in pre-manifest Huntington's disease Kubera, Katharina M. Schmitgen, Mike M. Hirjak, Dusan Wolf, Robert Christian Orth, Michael Neuroimage Clin Regular Article BACKGROUND: The expression of the HTT CAG repeat expansion mutation causes neurodegeneration in Huntington's disease (HD). Objectives: In light of the – mainly in-vitro – evidence suggesting an additional role of huntingtin in neurodevelopment we used 3T MRI to test the hypothesis that in CAG-expanded individuals without clinical signs of HD (preHD) there is evidence for neurodevelopmental abnormalities. METHODS: We specifically investigated the complexity of cortical folding, a measure of cortical neurodevelopment, employing a novel method to quantify local fractal dimension (FD) measures that uses spherical harmonic reconstructions. RESULTS: The complexity of cortical folding differed at a group level between preHD (n = 57) and healthy volunteers (n = 57) in areas of the motor and visual system as well as temporal cortical areas. However, there was no association between the complexity of cortical folding and the loss in putamen volume that was clearly evident in preHD. CONCLUSIONS: Our results suggest that HTT CAG repeat length may have an influence on cortical folding without evidence that this leads to developmental pathology or was clinically meaningful. This suggests that the HTT CAG-repeat expansion mutation may influence the processes governing cortical neurodevelopment; however, that influence seems independent of the events that lead to neurodegeneration. Elsevier 2019-06-29 /pmc/articles/PMC6627026/ /pubmed/31491822 http://dx.doi.org/10.1016/j.nicl.2019.101913 Text en © 2019 The Authors http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Regular Article Kubera, Katharina M. Schmitgen, Mike M. Hirjak, Dusan Wolf, Robert Christian Orth, Michael Cortical neurodevelopment in pre-manifest Huntington's disease |
title | Cortical neurodevelopment in pre-manifest Huntington's disease |
title_full | Cortical neurodevelopment in pre-manifest Huntington's disease |
title_fullStr | Cortical neurodevelopment in pre-manifest Huntington's disease |
title_full_unstemmed | Cortical neurodevelopment in pre-manifest Huntington's disease |
title_short | Cortical neurodevelopment in pre-manifest Huntington's disease |
title_sort | cortical neurodevelopment in pre-manifest huntington's disease |
topic | Regular Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6627026/ https://www.ncbi.nlm.nih.gov/pubmed/31491822 http://dx.doi.org/10.1016/j.nicl.2019.101913 |
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