Natural biological variation of white matter microstructure is accentuated in Huntington's disease
| Autor: | HE Crawford, Rachael I. Scahill, Sarah Gregory, Kiran K. Seunarine, Alexandra Durr, Douglas R. Langbehn, Sarah J. Tabrizi, Michael Orth, Blair R. Leavitt, Raymund A.C. Roos, Geraint Rees |
|---|---|
| Přispěvatelé: | University College of London [London] (UCL), University of British Columbia (UBC), Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Universiteit Leiden [Leiden], University of Iowa [Iowa City], Universität Ulm - Ulm University [Ulm, Allemagne], Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), HAL UPMC, Gestionnaire |
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Adult Male Genotype [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology Gene mutation Biology Neuropsychological Tests White matter 03 medical and health sciences 0302 clinical medicine Huntington's disease natural variability medicine Humans Radiology Nuclear Medicine and imaging Research Articles Genetic association Brain Mapping Huntingtin Protein Biological Variation Individual Radiological and Ultrasound Technology [SDV.NEU.NB] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology Cognition Middle Aged medicine.disease White Matter 030104 developmental biology medicine.anatomical_structure Huntington Disease Diffusion Tensor Imaging Neurology Female Neurology (clinical) Anatomy Age of onset Nerve Net Neuroscience 030217 neurology & neurosurgery Psychomotor Performance Diffusion MRI Tractography Research Article |
| Zdroj: | Human Brain Mapping, 39(9), 3516-3527 Human Brain Mapping Human Brain Mapping, Wiley, 2018, 39 (9), pp.3516-3527. ⟨10.1002/hbm.24191⟩ Human Brain Mapping, 2018, 39 (9), pp.3516-3527. ⟨10.1002/hbm.24191⟩ |
| ISSN: | 1065-9471 1097-0193 |
| DOI: | 10.1002/hbm.24191⟩ |
| Popis: | International audience; Huntington's disease (HD) is a monogenic neurodegenerative disorder caused by a CAG-repeat expansion in the Huntingtin gene. Presence of this expansion signifies certainty of disease onset, but only partly explains age at which onset occurs. Genome-wide association studies have shown that naturally occurring genetic variability influences HD pathogenesis and disease onset. Investigating the influence of biological traits in the normal population, such as variability in white matter properties , on HD pathogenesis could provide a complementary approach to understanding disease modification. We have previously shown that while white matter diffusivity patterns in the left senso-rimotor network were similar in controls and HD gene-carriers, they were more extreme in the HD group. We hypothesized that the influence of natural variation in diffusivity on effects of HD pathogenesis on white matter is not limited to the sensorimotor network but extends to cognitive, limbic, and visual networks. Using tractography, we investigated 32 bilateral pathways within HD-related networks, including motor, cognitive, and limbic, and examined diffusivity metrics using principal components analysis. We identified three independent patterns of diffusivity common to controls and HD gene-carriers that predicted HD status. The first pattern involved almost all tracts, the second was limited to sensorimotor tracts, and the third encompassed cognitive network tracts. Each diffu-sivity pattern was associated with network specific performance. The consistency in diffusivity patterns across both groups coupled with their association with disease status and task performance indicates that naturally-occurring patterns of diffusivity can become accentuated in the presence of the HD gene mutation to influence clinical brain function. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|