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D10 Neurofilament light protein in blood predicts regional atrophy in huntington’s disease
  1. Rachael I Scahill1,
  2. Eileanoir B Johnson1,
  3. Lauren M Byrne1,
  4. Sarah Gregory1,
  5. Filipe B Rodrigues1,
  6. Kaj Blennow2,
  7. Alexandra Durr3,
  8. Blair R Leavitt4,
  9. Raymund A Roos5,
  10. Henrik Zetterberg6,
  11. Sarah J Tabrizi1,
  12. Edward J Wild1,
  13. the TRACK-HD investigators
  1. 1HD Research Centre, UCL Institute of Neurology, London, UK
  2. 2Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden
  3. 3Institut du Cerveau et de la Moelle épinière (ICM), Sorbonne Universités, UPMC University Paris 06, UMRS_1127, INSERM, U 1127, CNRS, UMR 7225, APHP, Genetics Department, Pitié-Salpêtrière University Hospital, Paris, France
  4. 4Centre for Molecular Medicine and Therapeutics, University of British Columbia, Vancouver, BC, Canada
  5. 5Department of Neurology, Leiden University, Leiden, Netherlands
  6. 6Henrik Zetterberg, Department of Molecular Neuroscience, UCL Institute of Neurology, Queen Square, London, UK; Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden; Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden; UK Dementia Research Institute, London, UK

Abstract

Background Neurofilament light (NfL) protein in blood plasma has been proposed as a prognostic biomarker of neurodegeneration in a number of conditions, including Huntington’s disease (HD). Previous work has demonstrated elevated levels of NfL in HD gene expansion carriers when compared with controls, with NfL levels reflecting baseline motor and cognitive deficits as well as reduced global and regional brain volume. However, global measures provide limited insight into the regional distribution of NfL-associated pathology due to the HD gene mutation.

Aims This study aims to establish the regional distribution of NfL-associated pathology in HD using voxel-based morphometry (VBM).

Methods We examine associations between NfL measured in plasma and regionally-specific atrophy in cross-sectional (n=198) and longitudinal data (n=177) in HD gene expansion carriers from the international multisite TRACK-HD study. Using VBM we measured associations between baseline NfL levels and both baseline grey matter and white matter volume; and longitudinal change in grey matter and white matter over the subsequent three years in HD gene expansion carriers.

Results After controlling for demographics, associations between increased NfL levels and reduced brain volume were seen in cortical and subcortical grey matter and within the white matter. After also controlling for known predictors of disease progression (age and CAG repeat length), associations were limited to the caudate and putamen. Longitudinally, NfL predicted subsequent occipital grey matter atrophy and widespread white matter reduction, both before and after correction for other predictors of disease progression.

Conclusions These findings highlight the value of NfL as a dynamic marker of brain atrophy and, more generally, provide further evidence of the strong association between plasma NfL level, a candidate blood biomarker, and pathological neuronal change.

  • NfL
  • Atrophy
  • VBM

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