Intercellular transport of Tau protein and β-amyloid mediated by tunneling nanotubes

Tunneling nanotubes (TNTs) are thin channel-like structures connecting distant cells, providing a route for intercellular communication. In this study, we investigated the physical properties, including the cytoskeletal components, length and diameter, of the TNTs formed by HEK293T, U87 MG, and U251 cell lines. We found that organelles such as lysosomes, mitochondria, and Golgi bodies can be transported through TNTs, indicating that TNTs can mediate material transport. Moreover, we investigated the transport of the Tau protein and β-amyloid (Aβ), which are both closely related to Alzheimer's disease (AD) pathology, through TNTs. The results showed that TNTs formed by various neuronal cell lines can mediate the transport of different forms of the Tau protein and fluorescently labeled Aβ and that this transport is bidirectional, with different velocities in various cell lines. Our results confirmed the transport of the Tau protein and Aβ between cells and provided a possible explanation for the cascade of cell death in specific brain regions during the progression of AD. Our findings suggest new possibilities for the treatment of AD.