CSF neurofilament light chain reflects corticospinal tract degeneration in ALS

Objective: Diffusion tensor imaging (DTI) is sensitive to white matter tract pathology. A core signature involving the corticospinal tracts (CSTs) has been identified in amyotrophic lateral sclerosis (ALS). Raised neurofilament light chain protein (NfL) in cerebrospinal fluid (CSF) is thought to reflect axonal damage in a range of neurological disorders. The relationship between these two measures was explored. Methods: CSF and serum NfL concentrations and DTI acquired at 3 Tesla on the same day were obtained from ALS patients (n = 25 CSF, 40 serum) and healthy, age-similar controls (n = 17 CSF, 25 serum). Within-group correlations between NfL and DTI measures of microstructural integrity in major white matter tracts (CSTs, superior longitudinal fasciculi [SLF], and corpus callosum) were performed using tract-based spatial statistics. Results: NfL levels were higher in patients compared to controls. CSF levels correlated with clinical upper motor neuron burden and rate of disease progression. Higher NfL levels were significantly associated with lower DTI fractional anisotropy and increased radial diffusivity in the CSTs of ALS patients, but not in controls. Interpretation: Elevated CSF and serum NfL is, in part, a result of CST degeneration in ALS. This highlights the wider potential for combining neurochemical and neuroimaging-based biomarkers in neurological disease.