Scientists Have Finally Uncovered How Alzheimer's Spreads Through the Brain

A common brain protein may allow Alzheimer's disease to spread in an unexpected way, carrying toxic tau protein from damaged neurons to healthy ones. Researchers believe that by intercepting these harmful proteins before they reach new cells, it may one day be possible to slow the relentless progression of the disease.

Alzheimer's disease is characterized by the accumulation of a toxic protein called tau, which damages and ultimately kills brain cells. The disease worsens as this harmful protein spreads into new areas of the brain, leading to memory loss and cognitive decline.

Now, researchers have identified an unexpected player in this process. In a study of mice, they found that a brain protein called Arc—which normally helps neurons communicate—also appears to facilitate the spread of toxic tau from diseased brain cells to healthy ones.

This discovery points to a potential new strategy for slowing Alzheimer's disease. Rather than attempting to eliminate tau protein entirely, future therapies may aim to stop it from reaching healthy brain cells in the first place.

"I'm excited that we've identified a potential new way to halt the progression of Alzheimer's disease," said Dr. Jason Shepherd, professor of neurobiology at the University of Utah Health and senior author of the study.

The findings were published in the journal Cell.[1]

How Arc Helps Toxic Tau Move

To study how Alzheimer's spreads, researchers compared mouse models with and without the Arc protein. Their experiments showed that Arc is essential for moving toxic tau protein between neurons.

Under normal conditions, Arc plays an important role in brain function. The protein packages itself into tiny membrane-bound sacs called extracellular vesicles (EVs), which are transmitted from one neuron to another, carrying important cellular signals.

Researchers discovered that toxic tau protein can exploit this natural communication system. By attaching itself to Arc within these tiny vesicles, tau can move from an unhealthy neuron to a healthy one, where it can continue to propagate the disease.

Tau Protein Makes Healthy Brain Cells Toxic

Every neuron contains tau protein, but in Alzheimer's disease, this protein begins to aggregate into large, sticky tangles that disrupt the cell's internal transport system before eventually killing the neuron.

Dr. Mitali Tyagi, a postdoctoral research associate at Washington University in St. Louis and first author of the study, conducted this research as a graduate student in Shepherd's lab at U of U Health. She likens these tangles to "glue monsters."

"They stick together and block transport inside the neuron," Tyagi explained. "But they can break apart into smaller glue monsters, called tau seeds, which can then be transferred to new neurons. Once a tau seed encounters healthy tau, it can corrupt it. So, the pathological process starts all over again in a healthy neuron."

In Alzheimer's mouse models, the team found extracellular vesicles containing both Arc and "sticky" tau in brain tissue. These vesicles were able to enter healthy cells and trigger the formation of new tau tangles.

When Arc was removed, the picture changed dramatically. Extracellular vesicles from mice lacking Arc contained very little tau, and the disease could no longer spread efficiently to neighboring brain cells.

"When we removed Arc, we saw that tau transfer was severely, severely reduced," Tyagi said. "It almost disappeared."

Arc Has Both Harmful and Beneficial Roles

Although blocking Arc may seem like an obvious therapeutic strategy, researchers found that this protein also plays an important protective role in the early stages of the disease.

By helping neurons expel excess toxic tau, Arc appears to allow damaged cells to survive longer. In mice lacking Arc, toxic tau remained trapped inside neurons, causing those already sick cells to die more quickly.

"When Arc is absent, tau becomes trapped within neurons and accumulates to toxic levels. When Arc is present, tau can be released in extracellular vesicles," Tyagi said. While this helps reduce tau accumulation inside the original neuron, the released tau can be taken up by neighboring healthy neurons, promoting the spread of pathology.

These findings suggest that the most effective treatment may not be to stop diseased cells from releasing tau. Instead, it may be better to block these toxic extracellular vesicles from entering healthy neurons.

A Potential New Target for Alzheimer's Treatment

Researchers also identified extracellular vesicles containing both Arc and tau in human brain tissue, suggesting that the same mechanism may exist in humans. However, they emphasize that much more research is needed before any potential therapy can be applied to patients.

"The majority of what we've done has been in mice, not humans," Shepherd noted. "We have some clues that what happens in these mice might also happen in humans, but we don't know yet. We are a long way from saying we are developing a treatment for any disease. But it could open new avenues to get there."

One promising possibility is to intercept taucontaining extracellular vesicles after they leave diseased neurons, but before they reach healthy ones. While this approach would not reverse existing brain damage, it could potentially slow or prevent further spread of Alzheimer's disease.

"If we could target these specific EVs, that would be a very useful therapeutic strategy," Shepherd said. "For people with earlyonset Alzheimer's or dementia, if we could stop the spread, then we could prevent further damage and cognitive decline."

[1] Mitali Tyagi1, Eric de Hoog, Matthew Grega, et al. Arc mediates intercellular tau transmission via extracellular vesicles. Cell. 10.1016/j.cell.2026.06.008
https://www.cell.com/cell/fulltext/S0092-8674(26)00695-1