Neurons communicate at synapses, points where electrical and chemical signals pass from cell to cell. In other cell types, scientists have seen direct connections facilitated by slender membrane extensions called nanotubes, particularly tunneling nanotubes (TNTs) that transfer material between cells. TNTs have been reported in isolated brain neurons but their presence in mature brain tissue and functional role remained uncertain.
In a recent study, researchers reported a distinct form of nanotube that seems to act as a bridge, shuttling contents between dendrites—the branched processes of neurons. These “dendritic nanotubes,” or DNTs, were shown to be linked with the spread of amyloid‑beta (Aβ) peptides, a hallmark of Alzheimer’s disease.
Using advanced super‑resolution imaging (dSRRF) alongside electron microscopy, the team visualized actin‑rich DNTs linking dendrites in both mouse and human cortical samples. To confirm that these structures differ from other dendritic components, the investigators employed specialized imaging techniques and machine‑learning classification. The analysis revealed a unique morphology distinct from synaptic contacts, and live cultures demonstrated that DNTs form and collapse dynamically, possessing an internal architecture separate from other neuronal protrusions.
Unlike classic TNTs, DNTs do not form open tunnels; their termini are sealed, yet they still traffic calcium ions and small molecules across neurons. The researchers then explored whether DNTs could serve as conduits for amyloid‑beta. They introduced labeled Aβ into a single neuron within a mouse brain slice and observed its dissemination into nearby neurons via DNTs. When they blocked DNT formation pharmacologically, the spread of amyloid‑beta diminished markedly.
Computational modeling suggested that in mice modeled for Alzheimer’s, the density of DNTs rises before the appearance of amyloid plaques, hinting at a role early in disease progression. A computational analysis supported the view that hyperactive DNT networks could expedite toxic Aβ accumulation in specific neurons, providing a mechanistic link between nanotube changes and Alzheimer’s pathology.
While the discovery offers fresh insight into how Alzheimer’s may propagate at the cellular level, many questions remain about the broader functions of DNTs in brain health and disease. Future investigations will be essential to clarify their roles and evaluate whether targeting these structures could open new avenues for early diagnosis or intervention.
The study was published in Science and represents the result of collaborative research efforts.