**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.**
Isabel Cardoso 
Molecular Neurobiology, i3S - Instituto de Investigação e Inovação em Saúde, Porto, Portugal

**Main Body of the Abstract**
Alzheimer's disease (AD) is a complex neurodegenerative disorder involving alterations in multiple processes, molecular mechanisms, and proteins. Transthyretin (TTR) has been established as a protein with protective functions in the central and peripheral nervous systems, in addition to its very well-known transport functions. This study explored the neuroprotective role of TTR through in vitro assays using rat hippocampal neurons, and in vivo analysis using our exclusive AD mouse model (AβPPswe/PS1A246E) and non-transgenic (NT) animals, established in different TTR genetic backgrounds. We assessed the impact of TTR in cytoskeletal alterations namely cofilin-actin rod formation, and showed that TTR can revert or inhibit Aβ-induced rods, both in vitro and in vivo. Regarding synaptic structures, our study showed that Aβ decreases the number of active synapses, without affecting the levels of pre- and post-synaptic markers VGLUT1 and PSD-95, respectively. In contrast, TTR was shown to increase the levels of VGLUT1 and PSD-95, though its effect on active synapses was not significant. In our in vivo studies, although we found no neuronal loss in our mouse models up to 7 months, as evaluated by NeuN staining, nor related to the AD-like context nor TTR levels, we found astrogliosis, evaluated by GFAP staining, in mice with TTR reduction aged 7 months, showing a greater impact in AD/TTR than in NT/TTR mice.
In summary, TTR can protect against Aβ noxious effects, albeit the exact underlying mechanisms remain a complex topic that requires further investigation.



Unraveling the protection of neuronal cytoskeleton and synaptic structures by Transthyretin in Alzheimer's Disease PA90 (#79)

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.