SALT LAKE CITY — Researchers at University of Utah Health published a study in 2026 indicating that the Arc protein facilitates the spread of toxic Tau between brain cells in Alzheimer's disease. The study, titled "Arc mediates intercellular tau transmission via extracellular vesicles," appeared in the journal Cell.

The research team found that the Arc protein is necessary for the spread of toxic Tau between brain cells in mice. Toxic Tau proteins attach to Arc inside extracellular vesicles, which then travel from diseased neurons to healthy ones. The Arc protein normally packages itself into extracellular vesicles that transmit cellular signals between neurons.

Mitali Tyagi, a postdoctoral research associate at Washington University in St. Louis and the first author of the paper, conducted the research as a neuroscience graduate student in the Shepherd Lab at University of Utah Health. Tyagi said, "When Arc is present, Tau can be released in extracellular vesicles." She added, "While this helps reduce Tau buildup within the original neuron, the released Tau can be taken up by neighboring healthy neurons, promoting the spread of pathology." In Alzheimer's model mice that lacked the Arc protein, brain extracellular vesicles contained minimal Tau and did not spread the disease to new cells.

In Alzheimer's disease, Tau proteins clump into tangles inside neurons, disrupting internal transport and killing the cells. "They glue together and block transportation within the neuron," Tyagi said. These Tau tangles can break down into smaller units called Tau seeds, which can then transfer to new neurons. "But they can break down into smaller glue monsters, called Tau seeds, which can then get transferred to a new neuron," Tyagi said. When a Tau seed contacts healthy Tau in a new neuron, it causes healthy Tau to form new tangles. "And once this Tau seed comes into contact with healthy Tau, it is able to corrupt it," she said. "So, the pathology starts all over again in a healthy neuron." Tyagi noted that when Arc was removed, the transfer of Tau was severely reduced. "When we removed Arc, we saw that the transfer of Tau was severely, severely reduced," she said. "It was almost gone." She also stated, "When Arc is absent, Tau becomes trapped inside neurons and accumulates to toxic levels."

The researchers studied a mouse model of Alzheimer's disease with and without the Arc protein. Mice that lacked the Arc protein experienced faster death of sick neurons because toxic Tau remained trapped inside the cells. Researchers found extracellular vesicles containing both Arc and Tau in the brains of the Alzheimer's model mice.

Jason Shepherd, a professor of neurobiology at University of Utah Health and the senior author of the study, said the research was conducted in mice and it is not yet known if the same mechanism occurs in humans. "We have some clues that whatever is happening in these mice could also be happening in humans, but we don't know that yet," Shepherd said. "I'm excited by the fact that we've identified a new way of potentially stopping the progression of Alzheimer's disease." He added, "And we're far away from saying that we're developing a treatment for anything. But it could open new avenues to get to that point." Shepherd said, "If we could target these particular EVs, that would be a really useful therapy strategy." He noted, "For someone with early-onset Alzheimer's or dementia, if we could stop the spread, then we could prevent further damage and cognitive decline."