@article{10.1172/jci.insight.92641, author = {Peter McColgan AND Kiran K. Seunarine AND Sarah Gregory AND Adeel Razi AND Marina Papoutsi AND Jeffrey D. Long AND James A. Mills AND Eileanoir Johnson AND Alexandra Durr AND Raymund A.C. Roos AND Blair R. Leavitt AND Julie C. Stout AND Rachael I. Scahill AND Chris A. Clark AND Geraint Rees AND Sarah J. Tabrizi AND the Track-On HD Investigators}, journal = {JCI Insight}, publisher = {The American Society for Clinical Investigation}, title = {Topological length of white matter connections predicts their rate of atrophy in premanifest Huntington’s disease}, year = {2017}, month = {4}, volume = {2}, url = {https://insight.jci.org/articles/view/92641}, 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.}, number = {8}, doi = {10.1172/jci.insight.92641}, url = {https://doi.org/10.1172/jci.insight.92641}, }