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Serum neurofilament light chain in hereditary transthyretin amyloidosis: validation in real-life practice

Carroll, Antonia S; Razvi, Yousuf; O'Donnell, Luke; Veleva, Elena; Heslegrave, Amanda; Zetterberg, Henrik; Vucic, Steve; ... Reilly, Mary M; + view all (2024) Serum neurofilament light chain in hereditary transthyretin amyloidosis: validation in real-life practice. Amyloid 10.1080/13506129.2024.2313218. (In press). Green open access

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Abstract

BACKGROUND: Neurofilament light chain (NfL) has emerged as a sensitive biomarker in hereditary transthyretin amyloid polyneuropathy (ATTRv-PN). We hypothesise that NfL can identify conversion of gene carriers to symptomatic disease, and guide treatment approaches. METHODS: Serum NfL concentration was measured longitudinally (2015-2022) in 59 presymptomatic and symptomatic ATTR variant carriers. Correlations between NfL and demographics, biochemistry and staging scores were performed as well as longitudinal changes pre- and post-treatment, and in asymptomatic and symptomatic cohorts. Receiver-operating analyses were performed to determine cut-off values. RESULTS: NfL levels correlated with examination scores (CMTNS, NIS and MRC; all p < .01) and increased with disease severity (PND and FAP; all p < .05). NfL was higher in symptomatic and sensorimotor converters, than asymptomatic or sensory converters irrespective of time (all p < .001). Symptomatic or sensorimotor converters were discriminated from asymptomatic patients by NfL concentrations >64.5 pg/ml (sensitivity= 91.9%, specificity = 88.5%), whereas asymptomatic patients could only be discriminated from sensory or sensorimotor converters or symptomatic individuals by a NfL concentration >88.9 pg/ml (sensitivity = 62.9%, specificity = 96.2%) However, an NfL increment of 17% over 6 months could discriminate asymptomatic from sensory or sensorimotor converters (sensitivity = 88.9%, specificity = 80.0%). NfL reduced with treatment by 36%/year and correlated with TTR suppression (r = 0.64, p = .008). CONCLUSIONS: This data validates the use of serum NfL to identify conversion to symptomatic disease in ATTRv-PN. NfL levels can guide assessment of disease progression and response to therapies.

Type: Article
Title: Serum neurofilament light chain in hereditary transthyretin amyloidosis: validation in real-life practice
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.1080/13506129.2024.2313218
Publisher version: http://dx.doi.org/10.1080/13506129.2024.2313218
Language: English
Additional information: © The Authors 2023. Original content in this paper is licensed under the terms of the Creative Commons Attribution 4.0 International (CC BY 4.0) Licence (https://creativecommons.org/licenses/by/4.0/).
Keywords: ATTRv amyloidosis, longitudinal, neurofilament light chain, polyneuropathy, transthyretin
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Inflammation
URI: https://discovery.ucl.ac.uk/id/eprint/10187463
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