Journal article
Topological length of white matter connections predicts their rate of atrophy in premanifest Huntington's disease
JCI insight, Vol.2(8), e92641
04/20/2017
DOI: 10.1172/jci.insight.92641
PMCID: PMC5396531
PMID: 28422761
Abstract
We lack a mechanistic explanation for the stereotyped pattern of white matter loss seen in Huntington's disease (HD). While the earliest white matter changes are seen around the striatum, within the corpus callosum, and in the posterior white matter tracts, the order in which these changes occur and why these white matter connections are specifically vulnerable is unclear. Here, we use diffusion tractography in a longitudinal cohort of individuals yet to develop clinical symptoms of HD to identify a hierarchy of vulnerability, where the topological length of white matter connections between a brain area and its neighbors predicts the rate of atrophy over 24 months. This demonstrates a new principle underlying neurodegeneration in HD, whereby brain connections with the greatest topological length are the first to suffer damage that can account for the stereotyped pattern of white matter loss observed in premanifest HD.
Details
- Title: Subtitle
- Topological length of white matter connections predicts their rate of atrophy in premanifest Huntington's disease
- Creators
- Peter McColgan - Huntington's Disease AssociationKiran K. Seunarine - UCL Institute of Child HealthSarah Gregory - Huntington's Disease AssociationAdeel Razi - NED University of Engineering and TechnologyMarina Papoutsi - Huntington's Disease AssociationJeffrey D. Long - University of IowaJames A. Mills - Department of Psychiatry.Eileanoir Johnson - Huntington's Disease AssociationAlexandra Durr - Assistance Publique – Hôpitaux de ParisRaymund A. C. Roos - Leiden University Medical CenterBlair R. Leavitt - University of British ColumbiaJulie C. Stout - Monash UniversityRachael I. Scahill - Huntington's Disease AssociationChris A. Clark - UCL Institute of Child HealthGeraint Rees - Wellcome Centre for Human NeuroimagingSarah J. Tabrizi - Huntington's Disease AssociationTrack On HD Investigators
- Resource Type
- Journal article
- Publication Details
- JCI insight, Vol.2(8), e92641
- DOI
- 10.1172/jci.insight.92641
- PMID
- 28422761
- PMCID
- PMC5396531
- NLM abbreviation
- JCI Insight
- ISSN
- 2379-3708
- eISSN
- 2379-3708
- Publisher
- Amer Soc Clinical Investigation Inc
- Number of pages
- 16
- Grant note
- MR/L012936/1 / Medical Research Council; UK Research & Innovation (UKRI); Medical Research Council UK (MRC); European Commission MR/L012936/1 / MRC; UK Research & Innovation (UKRI); Medical Research Council UK (MRC) National Institute for Health Research (NIHR) University College London Hospitals (UCLH) Biomedical Research Centre (BRC) 100227/Z/12/Z / Wellcome Trust; European Commission 091593/Z/10/Z; 103437/Z/13/Z / Wellcome Trust; European Commission
- Language
- English
- Date published
- 04/20/2017
- Academic Unit
- Psychiatry; Biostatistics
- Record Identifier
- 9984280880302771
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