• Milou Berends, Anne F Brunger, Johan Bijzet, Bart-Jan Kroesen, Gea Drost, Fiete Lange, Charlotte E Teunissen, Sjors In 't Veld, Alexander Fje Vrancken, GansReinold O BROBDepartment of Internal Medicine, University Medical Center Groningen, Groningen, The Netherlands.Amyloidosis Center of Expertise, University Medical Center Groningen, Groningen, The Netherlands., Bouke P C Hazenberg, Paul A van der Zwaag, and Hans L A Nienhuis.
• Department of Internal Medicine, University Medical Center Groningen, Groningen, The Netherlands.
• Amyloid. 2024 Jun 1; 31 (2): 132141132-141.

ObjectiveTo evaluate serum neurofilament light chain (sNfL) as biomarker of disease onset, progression and treatment effect in hereditary transthyretin (ATTRv) amyloidosis patients and TTR variant (TTRv) carriers.MethodssNfL levels were assessed longitudinally in persistently asymptomatic TTRv carriers (N = 12), persistently asymptomatic ATTRv amyloidosis patients (defined as asymptomatic patients but with amyloid detectable in subcutaneous abdominal fat tissue) (N = 8), in TTRv carriers who developed polyneuropathy (N = 7) and in ATTRv amyloidosis patients with polyneuropathy on treatment (TTR-stabiliser (N = 20) or TTR-silencer (N = 18)). Polyneuropathy was confirmed by nerve conduction studies or quantitative sensory testing. sNfL was analysed using a single-molecule array assay.ResultssNfL increased over 2 years in persistently asymptomatic ATTRv amyloidosis patients, but did not change in persistently asymptomatic TTRv carriers. In all TTRv carriers who developed polyneuropathy, sNfL increased from 8.4 to 49.8 pg/mL before the onset of symptoms and before polyneuropathy could be confirmed neurophysiologically. In symptomatic ATTRv amyloidosis patients on a TTR-stabiliser, sNfL remained stable over 2 years. In patients on a TTR-silencer, sNfL decreased after 1 year of treatment.ConclusionsNfL is a biomarker of early neuronal damage in ATTRv amyloidosis already before the onset of polyneuropathy. Current data support the use of sNfL in screening asymptomatic TTRv carriers and in monitoring of disease progression and treatment effect.

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