Researchers have found that the Arc protein helps spread toxic Tau proteins from diseased to healthy brain cells in mice, according to a June 29 announcement. The study, published in Cell, suggests that targeting this process could help prevent the progression of Alzheimer's disease.
Jason Shepherd, professor of neurobiology at University of Utah Health and senior author on the study, said, "I'm excited by the fact that we've identified a new way of potentially stopping the progression of Alzheimer's disease."
The research team used a mouse model of Alzheimer's disease with and without Arc protein. They discovered that Arc is necessary for toxic Tau to spread between neurons. Normally, Arc acts as a messenger between brain cells by wrapping itself in extracellular vesicles (EVs) that transport information from one neuron to another. However, toxic Tau can attach to these EVs and move from sick neurons into healthy ones.
Mitali Tyagi, postdoctoral research associate at Washington University in St. Louis and first author on the paper, described how Tau tangles disrupt cell function: "They glue together and block transportation within the neuron... But they can break down into smaller glue monsters, called Tau seeds, which can then get transferred to a new neuron. And once this Tau seed comes into contact with healthy Tau, it is able to corrupt it. So, the pathology starts all over again in a healthy neuron." In mice lacking Arc protein, their brain EVs contained little or no Tau and could not spread the disease effectively. Tyagi said about these findings, "When we removed Arc, we saw that the transfer of Tau was severely, severely reduced... It was almost gone."
The researchers also noted potential complications for therapy development because blocking Arc may accelerate neuronal death by trapping toxic Tau inside sick cells instead of allowing its removal via EVs.
Human brain tissue samples were found to contain EVs with both Arc and Tau proteins as well; however, more research is needed before translating these findings into treatments for humans. Shepherd cautioned, "Most of the work we've been doing is in mice, not 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... But it could open new avenues to get to that point." He added about future therapies, "If we could target these particular EVs... then we could prevent further damage and cognitive decline."
