byKrystal Kasal, Phys.org

Neuronal nanotubes mediate intercellular transport and disease. Credit:Science(2025). DOI: 10.1126/science.adr7403

Neurons in the brain communicate with each other through synapses—connection points that allow the passage of electrical and chemical signals. In non-neuronal cells, direct cell-to-cell connections have been found to occur with the assistance of nanotube structures. In particular, tunneling nanotubes (TNT) have exhibited material exchange in some cell types. These TNTs have beendocumentedin dissociated neurons in the brain, but their presence and function in mature brain neurons was unclear.

Now, a group of scientists have identified a new type of nanotube that appears to be acting as a kind of bridge, transporting materials between dendrites—the branched projections onneurons. The study,publishedinScience, describes what the group calls "dendritic nanotubes" or DNTs and their possible relationship to the accumulation of the peptide amyloid-beta (Aβ), which is seen with Alzheimer'sdisease.

The DNTs were first identified in mouse and human brain tissue using superresolution microscopy (dSRRF) and electron microscopy. The actin-rich DNTs were seen connecting the dendrites in mouse and human cortex. To distinguish DNTs from other dendritic structures, the team used specialized imaging andmachine learning-based analysis.

"A machine learning–based classification confirmed that their shape was distinct from that of synaptic structures. In cultured neurons, we observed these nanotubes forming dynamically and confirmed that they possessed a distinct internal structure, setting them apart from other neuronal extensions," the study authors write.

These nanotubes also behaved differently than the better-known TNTs. DNTs did not exhibit the tunneling behavior TNTs use to transport materials. Instead, the ends were closed off, thus earning them a slightly different name. Still, the DNTs did transport materials, like calcium ions and small molecules.

The researchers wanted to determine if thesenanotubeswould transport amyloid-beta to assess whether they were capable of contributing to the onset or progression of Alzheimer's disease. To do this, they inserted amyloid-beta into a neuron in one of the slices of mouse brain. They found that the DNTs spread the amyloid-beta peptides into the surrounding neurons. To affirm that the DNTs were responsible for the spread, they then inhibited the nanotube formation, which then decreased the spread of amyloid-beta.

The team performed computational models to assess the impact of theamyloid-betatransfer. They found that DNT density increases before amyloid plaque formation in Alzheimer's model mice, suggesting a role in early disease.

"We found that the nanotube network was significantly altered early in the disease, even before the formation of amyloid plaques, a hallmark of AD. Ourcomputational modelsupported these findings, predicting that overactivation in the nanotube network could accelerate the toxic accumulation of amyloid in specific neurons, thereby providing a mechanistic link between nanotube alterations and the progression of AD pathology," they explain.

Still, much is unknown about these newfound structures. Future work can help to determine what other roles they may play in brain function and disease. This work offers some valuable new insights into how Alzheimer's disease may spread at the cellular level, opening avenues for early intervention when better understood.

© 2025 Science X Network

More information: Minhyeok Chang et al, Intercellular communication in the brain through a dendritic nanotubular network, Science (2025). DOI: 10.1126/science.adr7403 Dimitri Budinger et al, Hidden networks in the brain, Science (2025). DOI: 10.1126/science.aeb2962 , www.science.org/doi/10.1126/science.aeb2962 Journal information: Science