Characterizing White Matter in Huntington's Disease

Sarah Gregory*, Eileanoir Johnson, Lauren M. Byrne, Filipe B. Rodrigues, Alexandra Henderson, John Moss, David Thomas, Hui Zhang, Enrico De Vita, Sarah J. Tabrizi, Geraint Rees, Rachael I. Scahill, Edward J. Wild

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

8 Citations (Scopus)


Background: Investigating early white matter (WM) change in Huntington's disease (HD) can improve our understanding of the way in which disease spreads from the striatum.

Objectives: We provide a detailed characterization of pathology-related WM change in HD. We first examined WM microstructure using diffusion-weighted imaging and then investigated both underlying biological properties of WM and products of WM damage including iron, myelin plus neurofilament light, a biofluid marker of axonal degeneration-in parallel with the mutant huntingtin protein.

Methods: We examined WM change in HD gene carriers from the HD-CSFcohort, baseline visit. We used standard-diffusion magnetic resonance imaging to measure metrics including fractional anisotropy, a marker of WM integrity, and diffusivity; a novel diffusion model (neurite orientation dispersion and density imaging) to measure axonal density and organization; T1-weighted and T2-weighted structural magnetic resonance imaging images to derive proxy iron content and myelin-contrast measures; and biofluid concentrations of neurofilament light (in cerebrospinal fluid (CSF) and plasma) and mutant huntingtin protein (in CSF).

Results: HD gene carriers displayed reduced fractional anisotropy and increased diffusivity when compared with controls, both of which were also associated with disease progression, CSF, and mutant huntingtin protein levels. HD gene carriers also displayed proxy measures of reduced myelin contrast and iron in the striatum.

Conclusion: Collectively, these findings present a more complete characterization of HD-related microstructural brain changes. The correlation between reduced fractional anisotropy, increased axonal orientation, and biofluid markers suggest that axonal breakdown is associated with increased WM degeneration, whereas higher quantitative T2 signal and lower myelin-contrast may indicate a process of demyelination limited to the striatum.

Original languageEnglish
Pages (from-to)52-60
Number of pages9
JournalMovement Disorders Clinical Practice
Issue number1
Early online date11 Nov 2019
Publication statusPublished - 28 Nov 2019


  • Huntington's disease
  • MRI
  • neurofilament light (NfL)
  • white matter


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