Mitali Tyagi, Ph.D., has a vivid way of describing what happens in an Alzheimer’s-affected brain. The toxic Tau proteins that drive the disease, she says, are like "glue monsters" that clump together, blocking traffic within neurons until the cells die. Now, in research that could reshape how we fight this devastating disease, scientists have discovered a key to stopping those glue monsters from spreading: a brain protein called Arc.
Researchers at University of Utah Health and Washington University in St. Louis found that Arc — which normally acts as a vital messenger between brain cells — can be hijacked by toxic Tau to hitch a ride from sick neurons to healthy ones. As Tau spreads to new regions of the brain, symptoms worsen. But in mouse models of Alzheimer’s disease that lacked Arc, the transfer of Tau was "severely, severely reduced. It was almost gone," according to Tyagi, who led the study as a neuroscience graduate student in the Shepherd Lab at U of U Health.
"I'm excited by the fact that we've identified a new way of potentially stopping the progression of Alzheimer’s disease," says Jason Shepherd, Ph.D., professor of neurobiology at University of Utah Health and senior author of the study, which was published in the journal Cell.
The researchers found that Arc normally travels between neurons wrapped in tiny bubbles called extracellular vesicles (EVs), carrying important biological messages. But toxic Tau can cling to Arc and catch this ride to neighboring cells, where it corrupts healthy Tau and starts the process over again. In mice without Arc, those EVs contained barely any Tau — and couldn’t spread the disease.
Perhaps most promising: the team discovered that human brain tissue also contains EVs carrying both Arc and Tau, suggesting the same mechanism may be at work in people. That opens a door that didn’t exist before. Rather than trying to keep Tau trapped inside dying cells — which could actually speed their death — future therapies might intercept toxic Tau-containing vesicles "midflight," after they’ve left a sick cell but before they can infect a healthy one.
Shepherd is careful to temper enthusiasm with realism. "We're far away from saying that we're developing a treatment for anything," he says. "But it could open new avenues to get to that point." For the 6.5 million Americans living with Alzheimer’s — a number projected to nearly double by 2050 — those new avenues are exactly what researchers and families have been waiting for.