Neurofilament light protein in blood predicts regional atrophy in Huntington disease

Abstract

ObjectiveNeurofilament 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.MethodsWe 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.ResultsAfter 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.ConclusionsThese 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.

Huntingtin Lowering Strategies for Disease Modification in Huntington’s Disease

“…Plasma NfL also correlated with rates of brain atrophy and cognitive decline in HD patients and may predict disease onset in premanifest HD mutation carriers (Byrne et al, 2017). A recent report also demonstrated that plasma NfL predicts regional atrophy in the HD brain, suggesting that, with further development and regulatory validation, this may be a useful peripheral biomarker for future HD clinical trials (Johnson et al, 2018).…”

Neurological Disease in Lupus: Toward a Personalized Medicine Approach

“…As such, imaging biomarkers may play a role as our ability to quantify macrostructural and microstructural damage (Figure 3 ). Serum and CSF biomarkers of “brain damage,” such as ultrasensitive detection of neurofilament protein, have been developed as a surrogate marker for clinical trials in neuroinflammatory and neurodegenerative diseases ( 146 ). Thus the rapid progress in our understanding of both pathophysiology and biomarkers of neurolupus is providing a much-needed roadmap to advance the field.…”

Cerebrospinal fluid neurofilament light in suspected sporadic Creutzfeldt-Jakob disease

“…NFL enrichment in axons and its presence in synapses suggest that axonal injury and synaptic/neuronal death occurring in several neurodegenerative/neurological disorders may result in increased cerebrospinal fluid (CSF) NFL concentrations. Thus, increased body fluid NFL levels have been suggested to indicate neuroaxonal and white matter degeneration [4,5].…”