Cortical Microstructural Correlates of Plasma Neurofilament Light Chain in Huntington's Disease.

Introduction: Huntington's disease (HD) is a severe neurodegenerative disorder with no effective treatment. Minimally-invasive biomarkers such as blood neurofilament light chain (NfL) in HD are therefore needed to quantitatively characterize neuronal loss. NfL levels in HD are known to correlate with disease progression and striatal atrophy, but whether they also reflect cortical degeneration remains elusive. Methods: In a sample of 35 HD patients, we characterized the cortical macro (cortical thickness) and microstructural (increased intracortical diffusivity) correlates of plasma NfL levels. We further investigated whether NfL-related cortical alterations correlated with clinical indicators of disease progression. Results: Increased plasma NfL levels in HD reflected posterior-cortical microstructural degeneration, but not reduced cortical thickness (p < 0.05, corrected). Importantly, these imaging alterations correlated, in turn, with more severe motor, cognitive and behavioral symptoms. Conclusion: Plasma NfL levels may be useful for tracking clinically-meaningful cortical deterioration in HD. Additionally, our results further reinforce the role of intracortical diffusivity as a valuable imaging indicator in movement disorders.