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Neurology. 2018 Feb 20;90(8):e717-e723. doi: 10.1212/WNL.0000000000005005. Epub 2018 Jan 24.

Neurofilament light protein in blood predicts regional atrophy in Huntington disease.

Author information

1
From the Huntington's Disease Research Centre (E.B.J., L.M.B., S.G., F.B.R., S.J.T., R.I.S., E.J.W.), UCL Institute of Neurology, London, UK; Clinical Neurochemistry Laboratory (K.B., H.Z.), Sahlgrenska University Hospital, Mölndal, Sweden; Institut du Cerveau et de la Moelle épinière (A.D.), Sorbonne Universités, UPMC University Paris 06, UMRS 1127, INSERM, U 1127, CNRS, UMR 7225; APHP (A.D.), Genetics Department, Pitié-Salpêtrière University Hospital, Paris, France; Centre for Molecular Medicine and Therapeutics (B.R.L.), University of British Columbia, Vancouver, BC, Canada; Department of Neurology (R.A.R.), Leiden University, the Netherlands; Department of Molecular Neuroscience (H.Z.), UCL Institute of Neurology, Queen Square, London, UK; Department of Psychiatry and Neurochemistry (H.Z.), Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden; and UK Dementia Research Institute (H.Z.), London, UK.
2
From the Huntington's Disease Research Centre (E.B.J., L.M.B., S.G., F.B.R., S.J.T., R.I.S., E.J.W.), UCL Institute of Neurology, London, UK; Clinical Neurochemistry Laboratory (K.B., H.Z.), Sahlgrenska University Hospital, Mölndal, Sweden; Institut du Cerveau et de la Moelle épinière (A.D.), Sorbonne Universités, UPMC University Paris 06, UMRS 1127, INSERM, U 1127, CNRS, UMR 7225; APHP (A.D.), Genetics Department, Pitié-Salpêtrière University Hospital, Paris, France; Centre for Molecular Medicine and Therapeutics (B.R.L.), University of British Columbia, Vancouver, BC, Canada; Department of Neurology (R.A.R.), Leiden University, the Netherlands; Department of Molecular Neuroscience (H.Z.), UCL Institute of Neurology, Queen Square, London, UK; Department of Psychiatry and Neurochemistry (H.Z.), Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden; and UK Dementia Research Institute (H.Z.), London, UK. e.wild@ucl.ac.uk.

Abstract

OBJECTIVE:

Neurofilament light (NfL) protein in blood plasma has been proposed as a prognostic biomarker of neurodegeneration in a number of conditions, including Huntington disease (HD). This study investigates the regional distribution of NfL-associated neural pathology in HD gene expansion carriers.

METHODS:

We examined associations between NfL measured in plasma and regionally specific atrophy in cross-sectional (n = 198) and longitudinal (n = 177) data in HD gene expansion carriers from the international multisite TRACK-HD study. Using voxel-based morphometry, we measured associations between baseline NfL levels and both baseline gray matter and white matter volume; and longitudinal change in gray matter and white matter over the subsequent 3 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 gray 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 gray 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 pathologic neuronal change.

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