**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; and Westmead Amyloidosis Centre, Westmead Hospital, University of Sydney, Sydney, Australia

**Main Body of the Abstract**
Background: MScan-motor unit number estimation (MScan-MUNE) was evaluated to estimate axonal loss, as a potential biomarker of transition to symptomatic disease in hereditary transthyretin amyloid polyneuropathy (ATTRv-PN).
Methods: Ulnar MScan-MUNE was undertaken in 19 prospectively recruited patients carrying ATTR variants, and parameters were compared between patients with large fibre neuropathy (LF+), those without (LF-), and healthy controls. Relationships to clinical severity scores were determined and cut-off values calculated.
Results: Compared to healthy controls, despite similar motor amplitudes, LF+ patients had fewer motor units (51.8 ± 35.8 vs 102.8 ± 42.2, p=0.003) and large units (11.3 (9.4 - 15.6) vs 25.4 (18.3 - 33.8), p=0.007), and greater mean unit amplitude (146.8 ± 65.5 vs 99.7 ± 37.4, p=0.005). LF- patients had greater mean unit amplitude than healthy controls (117.0 ± 4.4 vs 84.2 ± 30.0, p<0.05). MScan-MUNE and the number of large units reduced with increasing disease severity (all p<0.05). A cut-off of 76 motor units could distinguish asymptomatic individuals (Polyneuropathy Disability (PND) Score 0) from symptomatic (PND 1 or greater; AUC 0.80 (0.54 - 1.00)) with sensitivity of 100% and specificity of 78.6%.
Conclusions: ATTRv-PN is associated with progressive axonal loss, measured by MScan-MUNE, that correlates with disease severity. Motor unit loss occurs early in ATTRv-PN, masked by re-innervation, which preserves CMAP amplitudes. MScan-MUNE may be a promising targeted biomarker of transition to symptomatic disease in ATTRv-PN.



**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; and Westmead Amyloidosis Centre, Westmead Hospital, University of Sydney, Sydney, Australia

**Main Body of the Abstract**
**Background:** MScan-motor unit number estimation (MScan-MUNE) was evaluated to estimate axonal loss, as a potential biomarker of transition to symptomatic disease in hereditary transthyretin amyloid polyneuropathy (ATTRv-PN).
**Methods:** Ulnar MScan-MUNE was undertaken in 19 prospectively recruited patients carrying ATTR variants, and parameters were compared between patients with large fibre neuropathy (LF+), those without (LF-), and healthy controls. Relationships to clinical severity scores were determined and cut-off values calculated.
**Results:** Compared to healthy controls, despite similar motor amplitudes, LF+ patients had fewer motor units (51.8 ± 35.8 vs 102.8 ± 42.2, p=0.003) and large units (11.3 (9.4 - 15.6) vs 25.4 (18.3 - 33.8), p=0.007), and greater mean unit amplitude (146.8 ± 65.5 vs 99.7 ± 37.4, p=0.005). LF- patients had greater mean unit amplitude than healthy controls (117.0 ± 4.4 vs 84.2 ± 30.0, p<0.05). MScan-MUNE and the number of large units reduced with increasing disease severity (all p<0.05). A cut-off of 76 motor units could distinguish asymptomatic individuals (Polyneuropathy Disability (PND) Score 0) from symptomatic (PND 1 or greater; AUC 0.80 (0.54 - 1.00)) with sensitivity of 100% and specificity of 78.6%.
**Conclusions**: ATTRv-PN is associated with progressive axonal loss, measured by MScan-MUNE, that correlates with disease severity. Motor unit loss occurs early in ATTRv-PN, masked by re-innervation, which preserves CMAP amplitudes.** **MScan-MUNE may be a promising targeted biomarker of transition to symptomatic disease in ATTRv-PN.



 Motor unit remodelling as an early biomarker of disease involvement in hereditary transthyretin amyloidosis  PB24 (#127)

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.