Scientists Uncover Mechanism Behind Alzheimer's Spread

Alzheimer's disease is characterized by the accumulation of a toxic protein called Tau, which destroys brain cells and leads to cognitive decline. In a healthy brain, Tau plays a standard structural role, but during the disease, it clumps into sticky tangles. Dr. Mitali Tyagi, a postdoctoral associate at Washington University, described these clusters as 'glue monsters' that disrupt internal cellular transport. Eventually, these tangles break down into smaller seeds, which travel to neighboring healthy neurons and corrupt their healthy proteins.

In a study published in the journal Cell, researchers at University of Utah Health investigated this spreading mechanism in mice. They discovered that Arc, a protein responsible for neuronal communication, is utilized by toxic Tau to travel between cells. Under normal conditions, Arc is packaged into tiny sacs called extracellular vesicles to carry signals to other neurons. However, experiments showed that toxic Tau attaches to Arc inside these vesicles, using them as vehicles to infect healthy cells.

By comparing mouse models, the team discovered that when the Arc protein was removed, the transmission of Tau was almost entirely stopped. Despite this finding, the researchers realized that Arc also plays a protective role in the early stages of the disease. When Arc is present, it helps sick cells expel excess Tau, allowing them to survive longer than they would without it. If Arc were completely blocked in patients, Tau would remain trapped inside neurons, causing them to die much faster.

Consequently, scientists believe that instead of preventing Tau release, future therapies should block these toxic vesicles from entering healthy neurons. The research team also detected similar vesicles containing both Arc and Tau in human brain samples, suggesting a similar process in humans. Senior author Jason Shepherd, a professor of neurobiology, noted that while these findings were promising, clinical treatments remained far in the future.