Researchers report that the neuronal protein Arc can help move disease-linked tau between brain cells by packaging it into extracellular vesicles, a mechanism observed in mouse experiments and supported by findings in human brain tissue. The work, published in Cell, suggests that therapies might one day aim to block these vesicles from entering healthy neurons to slow progression—though the approach remains far from clinical use.
A protein best known for helping neurons communicate may also aid the spread of tau pathology linked to Alzheimer’s disease, researchers at University of Utah Health report.
In a study published in Cell, the team found that Arc—an activity-regulated neuronal protein—can help load human tau into tiny membrane-bound particles called extracellular vesicles (EVs). Those EVs can then be taken up by other neurons, where they can promote tau “seeding,” the process by which misfolded tau triggers additional tau aggregation.
To test Arc’s role, the researchers compared tauopathy-model mice that had Arc with otherwise similar mice engineered to lack the protein. In the Arc-deficient animals, EVs contained markedly less tau and were less able to drive tau aggregation, and the experiments indicated that intercellular tau transmission was strongly reduced.
The researchers also describe Arc as having a potentially protective effect for the neuron releasing tau: when Arc was absent, tau accumulated inside neurons and was associated with faster neuron loss in affected brain regions in the mouse model. That finding suggests that completely blocking Arc itself could worsen injury to already-damaged cells.
Instead, the authors argue that a more plausible therapeutic strategy—if the mechanism holds in people—would be to prevent tau-containing EVs from entering healthy neurons after they are released. Such an approach would be aimed at slowing additional spread, not reversing damage that has already occurred.
The team also reported detecting EVs containing both Arc and tau in human brain tissue, which they say is consistent with the same pathway operating in humans. They cautioned, however, that most of the evidence in the study comes from mouse experiments and that substantially more research would be needed before any treatment could be developed or tested in patients.
