A newly identified protein in the brain may play a key role in how Alzheimer's disease progresses. Research conducted at University of Utah Health has found that in mice, the Arc protein facilitates the spread of toxic Tau protein from diseased cells to healthy ones.
The role of Arc protein
The buildup of toxic Tau is known to kill neurons, and as this protein spreads to new regions of the brain, symptoms typically worsen. The study suggests that if therapies can be designed to target this specific spread, it could serve as a powerful tool to halt the progression of the disease.
Mechanism of protein transport
The research team found that Arc normally acts as a messenger between brain cells by traveling in microscopic bubbles known as extracellular vesicles or EVs. However, toxic Tau can attach to Arc to move from a sick neuron to a healthy one.
Tau tangles and neuron corruption
Mitali Tyagi, PhD, a postdoctoral research associate at Washington University in St. Louis and first author of the study, described Tau tangles as glue monsters that block transportation within neurons. These tangles can break down into smaller seeds that transfer to new neurons and corrupt healthy Tau.
Impact of Arc on cell survival
In mouse models lacking the Arc protein, researchers observed that the transfer of Tau was severely reduced. However, the protein also appears to serve a protective role in early disease stages. While Arc helps spread Tau, it also helps sick cells stay alive longer by exporting excess toxic Tau. In mice lacking Arc, Tau accumulates inside neurons at toxic levels, causing the cells to die faster.
Human implications for research
While the study was conducted in mice, the team found that human brain tissue also contains extracellular vesicles including both Arc and Tau, suggesting a similar mechanism may exist in humans.
Future therapeutic possibilities
Jason Shepherd, PhD, a professor of neurobiology at University of Utah Health and senior author on the study, noted that while they are far from developing a treatment, this could open new avenues for research. He expressed interest in the possibility of future therapies that block toxic Tau-containing vesicles mid-flight to prevent further cognitive decline and damage.
