Luis F Maia1,2,3, Aleksandra Maceski4, Isabel Conceição5, Laura Obici6, Rui Magalhães3, Andreas Cortese7, David Leppert4, Giampaolo Merlini6, Jens Kuhle4, Maria João Saraiva1. 1. Molecular Neurobiology Group, Instituto de Biologia Molecular e Celular (IBMC) - Instituto de Investigação e Inovação em Saúde (i3S) da Universidade do Porto, Porto, Portugal. 2. Neurology Department, Centro Hospitalar Universitário do Porto (CHUP), Porto, Portugal. 3. Instituto de Ciências Biomédicas Abel Salazar (ICBAS), Universidade do Porto, Porto, Portugal. 4. Neurologic Clinic and Policlinic, Departments of Medicine, Biomedicine and Clinical Research, University Hospital Basel, University of Basel, Basel, Switzerland. 5. Neurology Department, Centro Hospitalar Universitário Lisboa Norte (CHULN) and Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal. 6. Amyloidosis Research and Treatment Centre, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy. 7. Department of Brain and Behavioral Sciences, University of Pavia, Pavia, Italy.
Abstract
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.
Background: Transthyretin amyloidosis due to V30M mutation (ATTR-V30M) is the most frequent hereditary ATTRamyloidosis. 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-V30Mpatients stratified by clinical severity using a cross-sectional retrospective study design. Methods: Sixty ATTR-V30Mpatients 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-V30Mpatients 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.
Authors: Antonia Carroll; P James Dyck; Mamede de Carvalho; Marina Kennerson; Mary M Reilly; Matthew C Kiernan; Steve Vucic Journal: J Neurol Neurosurg Psychiatry Date: 2022-03-07 Impact factor: 13.654