Serum neurofilament light chain as a reliable biomarker of hereditary transthyretin-related amyloidosis - A Swiss reference center experience.

BACKGROUND AND AIMS
Hereditary transthyretin-related (hATTR) amyloidosis is a rare disease, causing a disabling and life-threatening axonal length-dependent polyneuropathy. Monitoring of disease progression and treatment response is difficult. We aimed to determine if serum neurofilament light chain (sNfL) is a reliable and early biomarker of peripheral neuropathy in hATTR amyloidosis.


METHODS
We prospectively included 20 hATTR patients, 14 symptomatic and 6 asymptomatic. Patients were assessed at baseline and one year, including a full clinical examination with disease severity and functional scores, electrochemical skin conductance measurement with Sudoscan® and nerve conduction studies, and sNfL level. hATTR patient sNfL were also compared with sNfL of 4532 healthy controls of a reference database by calculating age and BMI adjusted Z scores.


RESULTS
At baseline, median sNfL concentration was 3.6-fold higher in symptomatic than asymptomatic hATTR patients (p=0.003), and this difference was also found in our under 60-years-old patients (p=0.003). There was no significant difference of sNfL concentration between asymptomatic patients and healthy controls (Z-score of -0.29), but a significant difference between symptomatic patients and healthy controls (Z-score of 2.52). We found a significant correlation between sNfL levels and most clinical and electrophysiological disease severity scores, the strongest correlation being with the NIS score.


INTERPRETATION
sNfL seems to be a reliable biomarker of peripheral neuropathy severity in hATTR amyloidosis and can distinguish between asymptomatic and symptomatic patients. sNfL could also become a reliable biomarker to establish disease onset and treatment response. This article is protected by copyright. All rights reserved.