Photo Credit: Ralwel
The following is a summary of “A 14-year longitudinal study of neurofilament light chain dynamics in premanifest and transitional Huntington’s disease,” published in the October 2024 issue of Neurology by Voysey et al.
Neurofilament light chain (NfL) is increasingly recognized as a prognostic biomarker for Huntington’s disease (HD) in people with the gene mutation before symptoms appear.
Researchers conducted a retrospective study investigating NfL dynamics and predictive power in premanifest HD over 14 years.
They measured serum NfL levels using ultrasensitive immunoassays at 4 time points over 14 years in HD gene carriers (n = 21) and controls (n = 14). Gene carriers were pre-symptomatic at baseline. Clinical features were evaluated using the Unified Huntington’s Disease Rating Scale (UHDRS TMS), Montreal Cognitive Assessment (MoCA), Trail A/B task, Symbol Digit Modalities Task, and fluency tasks.
The results showed 14 out of 21 gene carriers transitioned to prodromal or manifest disease by the final timepoint (“converters”), NfL levels were higher in converters compared to non-converters and controls at all timepoints (P<0.001–0.03, ηp2 = 0.25–0.66). The rate of NfL increase was higher in converters than in non-converters (P=0.03) and controls (P=0.001). Baseline NfL accurately predicted conversion (area under the curve = 1.000, P=0.003). A higher NfL increase rate was linked to more severe motor symptoms (UHDRS-TMS p = 0.007, β = 0.711, R2= 0.468) and cognitive decline (MoCA P=0.007, β = −0.798, R2 = 0.604; Trail B, P=0.007, β = 0.772, R2 = 0.567; phonemic fluency p = 0.035, β = −0.632, R2 = 0.345). The study concluded that NfL levels rise more rapidly in those closer to Huntington’s disease onset, identifying individuals at risk for conversion and predicting clinical decline up to 10 years before onset.
They suggested that NfL levels rose more rapidly in individuals nearing HD onset and can predict clinical progression over a decade in advance.
Source: link.springer.com/article/10.1007/s00415-024-12700-x
