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 been documented in 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 on neurons. The study, published in Science, 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's disease.
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 and machine 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.
Serial axial planes of nonsynaptic dendritic
filopodium along the whole contacting ranges to the other dendrite in the
EM-resolved human brain (DF1; figs. S2A and S3A; H01 dataset). Axial step
distance = 33 nm. Scale bar = 500 nm. Credit: Science (2025).
DOI: 10.1126/science.adr7403
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 these nanotubes would
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 the amyloid-beta transfer.
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.
Our computational model supported
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.
by Krystal
Kasal, Phys.org
edited by Gaby
Clark, reviewed by Robert Egan
Source: Scientists
identify a new dendritic nanotubular network in the brain that may contribute
to Alzheimer's disease
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