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| Item Type: | Preprint |
|---|---|
| Title: | IgLON5 autoimmune antibodies activate Tau via neuronal hyperactivity |
| Creators Name: | Askin, B., Kilic, C., Cordero Gómez, C., Duong, S.L.L., Domingues-Baquero, A., Goihl, A., Nalbach, K., Petuschi, J., Grundschöttel, P., Wagner, J., Thomas, V., Lamberty, J., Withers, E., Huber, H., Huebschmann, S., Semenova, E., Turko, P., Newman, A.G., Diez, L., De Domenico, E., Körtvelyessy, P., Reinhold, D., Schneider, A., Neher, J.J., Ulas, T., Lichtenthaler, S.F., Rost, B.R., Schmitz, D., Prüss, H. and Wegmann, S. |
| Abstract: | Anti-IgLON5 disease is an autoimmune disease, in which autoantibodies (AABs) against the neuronal cell surface protein IgLON5 lead to profound brain dysfunction and Tau pathology. How α-IgLON5 AABs cause neuronal Tau protein pathology and neurodegeneration remains unclear. We find that patient-derived α-IgLON5 AABs cluster IgLON5 proteins with other cell surface proteins, leading to neuronal hyperactivity that triggers pathological Tau missorting and phosphorylation, typically observed early in Tau-related neurodegenerative diseases. In wildtype mice, α-IgLON5 AABs induce hippocampal Tau phosphorylation and neuroinflammatory responses. Our findings establish a causal link between the α-IgLON5 AABs and Tau pathology in anti-IgLON5 disease patients, and highlight the role of neuronal hyperactivity as a disease-overarching driver of Tau pathology and provide a potential target for therapeutic intervention. |
| Keywords: | Animals, Mice |
| Source: | bioRxiv |
| Publisher: | Cold Spring Harbor Laboratory Press |
| Article Number: | 2024.03.10.584272v2 |
| Date: | 5 December 2025 |
| Additional Information: | ProteomeXchange dataset PXD066225 has been reserved by the PRIDE repository for a dataset that has been deposited, but is not yet publicly released and announced to ProteomeXchange. |
| Official Publication: | https://doi.org/10.1101/2024.03.10.584272 |
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