Correlation between neuropathy severity and neurofilament light chain levels in Brazilian patients with hereditary transthyretin amyloidosis

Hereditary transthyretin amyloidosis (ATTRv) is a genetic disorder caused by more than 100 autosomal dominant mutations in the TTR gene. Owing to its marked clinical heterogeneity-particularly in its cardiac manifestations-ATTRv is frequently underdiagnosed and requires comprehensive clinical evaluation. The disease commonly presents as a progressive axonal sensorimotor polyneuropathy with autonomic involvement. Despite advances in disease-modifying therapies, including the availability of Tafamidis, delayed diagnosis remains a major challenge, contributing to increased morbidity and mortality. Therefore, the identification of reliable biomarkers for early detection, disease staging, and therapeutic monitoring is essential. One promising candidate is neurofilament light chain (NfL), a structural axonal protein released into the circulation following neuronal injury, which has been proposed as a biomarker of neuroaxonal damage in ATTRv in other populations. The present study aimed to evaluate plasma NfL (pNfL) levels in Brazilian patients with ATTRv and to investigate their association with neuropathy severity. Symptomatic and asymptomatic patients with genetically confirmed ATTRv followed at a specialized university reference center were included, along with healthy volunteer controls. A subgroup of symptomatic patients was receiving Tafamidis therapy. Clinical and demographic data were collected during routine visits, and neuropathy severity was assessed using validated instruments, including the Neuropathy Impairment Score (NIS) and the Polyneuropathy Disability (PND) score. Plasma NfL concentrations were measured using the ultrasensitive SIMOA SR-X platform. Statistical analyses were performed to compare pNfL levels across groups and to assess correlations with clinical parameters. Symptomatic patients not receiving Tafamidis exhibited significantly higher pNfL levels compared with treated symptomatic patients, asymptomatic mutation carriers, and healthy controls. Moreover, pNfL concentrations showed a positive correlation with NIS scores, indicating increasing axonal damage with disease progression. Z-score analyses further supported the ability of pNfL to discriminate between disease stages. In conclusion, plasma NfL emerges as a promising biomarker for assessing disease severity, progression, and treatment response in ATTRv, supporting its potential utility in Brazilian clinical practice.