# Exploratory Evaluation of the Predictive Value of Serum Neurofilament Light Chain for Autonomic Neuropathy in Hereditary Transthyretin Amyloidosis

## TL;DR

This study explores whether a blood marker called sNfL can predict autonomic neuropathy in a type of amyloidosis disease, but finds limited evidence.

## Contribution

The study is the first to explore the predictive value of sNfL for autonomic neuropathy in hereditary transthyretin amyloidosis.

## Key findings

- Individuals with autonomic neuropathy had significantly higher median sNfL levels.
- Multivariable analysis showed peripheral neuropathy, not autonomic neuropathy, predicted sNfL status.
- Receiver operating characteristic analysis suggested potential but had wide confidence intervals.

## Abstract

Background/Objectives: Serum neurofilament light chain (sNfL) is a biomarker for peripheral neuropathy as sNfL correlates with polyneuropathy severity in hereditary transthyretin (ATTRv) amyloidosis. It is unclear whether sNfL also correlates with autonomic neuropathy (ANP). In this exploratory study, we aimed to evaluate the value of sNfL as marker for ANP in patients with ATTRv amyloidosis. Methods: sNfL was measured retrospectively in 10 pathogenic transthyretin gene variant (TTRv) carriers and 28 patients with ATTRv amyloidosis. All 38 individuals underwent a comprehensive evaluation for ANP. Results: Individuals with ANP had a higher median sNfL level compared to those without ANP (p < 0.001). In univariable logistic regression analysis, age-adjusted sNfL status (normal versus abnormal for age) was associated with sex, ANP, and peripheral neuropathy. In multivariable logistic regression analysis, only peripheral neuropathy significantly predicted age-adjusted sNfL status (normal versus abnormal for age), and no signal was detected for ANP. Receiver operating characteristic analysis showed a considerable area under the curve for ANP. However, the confidence interval was wide for both analyses and only four cases with isolated ANP were included. Conclusions: Therefore, in this exploratory cohort, sNfL could not be identified as a marker for ANP, and larger studies are needed to clarify its value.