Tiny brain nanotubes found by Johns Hopkins may spread Alzheimer’s

Their experiments, which used genetically modified mice and advanced imaging tools, were supported by the National Institutes of Health and published on Oct. 2 in Science. According to the team, the discovery could deepen scientific understanding of how Alzheimer’s disease and other neurodegenerative disorders develop, offering potential pathways for new treatments.

In the study, the scientists observed that these microscopic tubes, known as nanotubes, primarily formed to help neurons expel toxic small molecules such as amyloid-beta. This protein can clump together into sticky plaques, one of the defining features of Alzheimer’s disease.

“Cells have to get rid of toxic molecules, and by producing a nanotube, they can then transmit this toxic molecule to a neighbor cell,” says corresponding author Hyungbae Kwon, associate professor of neuroscience at the Johns Hopkins University School of Medicine. “Unfortunately, this also results in spreading harmful proteins to other areas of the brain.”

With the help of powerful microscopes and live-cell imaging, the team watched as neurons created long, slender extensions between their dendrites — the branching projections that connect brain cells. These “dendritic nanotubes,” as the researchers call them, appeared to shuttle harmful molecules from one neuron to another.

“The long and thin column-like structures of these dendritic nanotubes help transfer information quickly from neuron to neuron,” says Kwon. “These nanotubes can transport calcium, ions or toxic molecules, and are ideal for sending information to cells that are far away.”

Computer simulations of the process mirrored the early stages of amyloid buildup, or “early amyloidosis,” and revealed what the researchers describe as a “nanotubular connectivity layer” that adds a new dimension to how brain cells interact.

Kwon notes that these insights could help scientists refine approaches to treating Alzheimer’s and similar conditions.

To explore the phenomenon, the researchers collected small brain tissue samples from healthy mice and examined them with high-resolution microscopy, allowing them to visualize the nanotubes in remarkable detail and track how they moved materials between neurons.

They then compared these samples with brain tissue from mice genetically engineered to develop Alzheimer’s-like amyloid buildup.

The researchers say the mice with Alzheimer’s disease had an increased number of nanotubes in their brains at three months old, when the mice were symptom-free, as compared with normal mice of the same age. At six months of age, the number of nanotubes in normal mice and those with Alzheimer’s disease began to equalize.

By taking a closer look at human neurons (sampled with permission from a publicly available electron microscopy database), the scientists identified nanotubes with similar morphology forming between neurons in the same way that the laboratory mice developed them.

In future experiments, Kwon says, the team will focus on whether larger-scale nanotube networks exist in cell types other than neurons in the brain. Eventually, he intends to design an experiment in which researchers create a nanotube to see how it affects the state of cells.

With such knowledge, Kwon says, there’s the possibility of one day dialing up or down nanotube production to protect the brain.

“When designing a potential treatment based on this work, we can target how nanotubes are produced — by either increasing or decreasing their formation — according to the stage of the disease,” Kwon says.

Funding for this research was provided by the National Institutes of Health (DP1MH119428 and R01NS138176).

Additional researchers who conducted the study are Minhyeok Chang, Sarah Krüssel, Juhyun Kim, Daniel Lee, Alec Merodio and Jaeyoung Kwon from Johns Hopkins; and Laxmi Kumar Parajuli and Shigeo Okabe from the University of Tokyo, Japan.