A 14-year longitudinal study of neurofilament light chain dynamics in premanifest and transitional Huntington’s disease

Background Growing evidence supports the value of neurofilament light (NfL) as a prognostic biomarker in premanifest Huntington’s disease (HD). To date, however, there has been no longitudinal study exceeding 3 years examining either its serial dynamics or predictive power in HD. We aimed to conduct the first such study. Methods Serum NfL was sampled using ultrasensitive immunoassay at four timepoints across a 14-year period in a cohort of HD gene carriers ( n = 21) and controls ( n = 14). Gene carriers were premanifest at baseline. Clinical features of HD were evaluated by Unified Huntington’s Disease Rating Scale (UHDRS TMS), Montreal Cognitive Assessment (MoCA), Trail A/B task, Symbol Digit Modalities Task and semantic/phonemic fluency tasks. Results 14/21 HD gene carriers converted to prodromal or manifest disease by the final timepoint (“converters”). At baseline and each subsequent timepoint, NfL levels were higher in converters than in non-converters and controls ( p = 10 years from disease onset.