Plasma neurofilament light chain: an early biomarker for hereditary ATTR amyloid polyneuropathy

Luis F. Maia, Aleksandra Maceski, Isabel Conceição, Laura Obici, Rui Magalhães, Andreas Cortese, David Leppert, Giampaolo Merlini, Jens Kuhle, Maria João Saraiva

Research output: Contribution to journalArticlepeer-review


Background: Transthyretin amyloidosis due to V30M mutation (ATTR-V30M) is the most frequent hereditary ATTR amyloidosis. Besides neurophysiological measures, there are no biomarkers to detect preclinical disease or monitor disease progression. CSF or plasma neurofilament light chain (pNfL) have recently been considered sensitive biomarkers to quantitate neuro-axonal damage in several disorders of the peripheral and central nervous system. Objective: Characterise plasma NfL levels in a series of untreated ATTR-V30M patients stratified by clinical severity using a cross-sectional retrospective study design. Methods: Sixty ATTR-V30M patients and 16 controls from 2 independent cohorts were analysed for pNfL by single-molecule array assay (SIMOA) technique. Disease severity was assessed with Polyneuropathy Disability Score. Results: pNfL is elevated in ATTR-V30M patients as a function of disease severity in both cohorts. Moreover, pNfL discriminates asymptomatic mutation carriers from early symptomatic patients (AUC = 0.97; p <.001) with high sensitivity (92.3%) and specificity (93.8%). pNfL elevation (>66.9 pg/mL) also discriminates patients with sensory neuropathy from patients with motor neuropathy (AUC = 0.91; p <.01) with a sensitivity of 61.5% and a specificity of 92.3%. Conclusion: pNfL is an easily accessible biomarker to establish ATTR-V30M disease conversion and to monitor disease progression. pNfL could be used as efficacy measure of disease-oriented therapies in clinical and pre-clinical trials.

Original languageEnglish
Publication statusAccepted/In press - Jan 1 2020


  • ATTR
  • biomarker
  • neurofilament light chain
  • plasma
  • transthyretin

ASJC Scopus subject areas

  • Internal Medicine


Dive into the research topics of 'Plasma neurofilament light chain: an early biomarker for hereditary ATTR amyloid polyneuropathy'. Together they form a unique fingerprint.

Cite this