Background Neurofilament light protein (NfL) has emerged as the leading biomarker candidate for disease progression and early detection of adult-onset Huntington’s Disease (HD). Juvenile-onset Huntington’s disease (JOHD) is a rare and particularly devastating form of Huntington’s disease (HD) for which clinical diagnosis is challenging and robust outcome measures are lacking.

Aim 1) Evaluate plasma NfL as a biomarker of HD in children 2) develop a method for remote NfL quantification to facilitate frequent monitoring, using at-home finger-prick blood collections.

Methods We performed a retrospective analysis of samples and data collected between 2009 and 2020 from the Kids-HD and Kids-JHD studies. Matched blood plasma and serum was collected from both venipuncture and finger-prick. NfL concentrations were quantified using ultrasensitive immunoassay.

Results We report elevated plasma NfL concentrations in JOHD and premanifest HD mutation-carrying children. In pediatric HD mutation carriers who were within 20 years of their predicted onset and patients with JOHD, plasma NfL level was associated with caudate and putamen volumes. Preliminary data of this novel finger-prick blood collection method for NfL quantification shows strong agreement with NfL levels from the venous blood gold standard.

Conclusions Quantifying plasma NfL concentration may assist clinical diagnosis and therapeutic trial design in the pediatric population. Remote blood collection may be used to study NfL in large numbers of HD mutation carriers and Juvenile-onset HD patients at-home with frequent sampling.