**Author Listing - Lead/ Submitting Author (we will be communicating with this individual): Name, Institution, City and State where the work was done. Co-authors will be added in a separate section.**
Antonia S Carroll. Brain and Mind Centre, Faculty of Medicine and Health, Translational Research Collective University of Sydney, Sydney, Australia

**Main Body of the 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 < 0.01) and increased with disease severity (PND and FAP; all p < 0.05). NfL was higher in symptomatic and sensorimotor converters, than asymptomatic or sensory converters irrespective of time (all p < 0.05). Symptomatic or sensorimotor converters were discriminated from asymptomatic patients by NfL concentrations > 64.5pg/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% per year and correlated with TTR suppression (r = 0.64, p = 0.008).
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.



**Author Listing - Lead/ Submitting Author (we will be communicating with this individual): Name, Institution, City and State where the work was done. Co-authors will be added in a separate section.**
Antonia S Carroll. Brain and Mind Centre, Faculty of Medicine and Health, Translational Research Collective University of Sydney, Sydney, Australia

**Main Body of the 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 < 0.01) and increased with disease severity (PND and FAP; all p < 0.05). NfL was higher in symptomatic and sensorimotor converters, than asymptomatic or sensory converters irrespective of time (all p < 0.05). Symptomatic or sensorimotor converters were discriminated from asymptomatic patients by NfL concentrations > 64.5pg/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% per year and correlated with TTR suppression (r = 0.64, p = 0.008).
**_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.



Serum Neurofilament light chain in hereditary transthyretin amyloidosis: Validation in real-life practice PB25 (#128)

We invite you to attend the XIX International Symposium on Amyloidosis to be held in Rochester, MN.

This symposium is organized as a hybrid meeting (with the focus on in-person) held from Sunday, May 26 through Thursday, May 30, 2024.

Together with the ISA Board and members of Mayo Clinic, a very attractive scientific hybrid program is being planned. The program will cover a variety of types of systemic amyloidosis: ATTR (hereditary and wild-type), AL (light-chain), AA and less frequent forms. There will be key lectures, specific symposia including those company sponsored, oral presentations and poster sessions of accepted abstracts.

COURSE DESCRIPTION
This program will provide a comprehensive review of state-of-the-art education in systemic amyloidosis: basic science, pathophysiology, diagnosis, current and emerging treatments. Scientific presentations will include competitive oral and poster abstracts. The rapid evolution of scientific discovery and expanding treatment options has created tremendous interest in the field and this meeting will fill and important gap in educating scientists and clinicians.