Scientists Discover the Brain Protein That Helps Alzheimer’s Spread Through the Brain

Researchers have identified distinct protein-based mechanisms that facilitate the spread of neurodegenerative diseases. In Alzheimer’s disease, the protein Arc acts as a delivery vehicle for toxic Tau, helping it spread from one neuron to another. Separately, research into Parkinson’s disease has identified two proteins on the surface of motor neurons that may act as entry points for toxic α-synuclein. These findings offer potential new targets for slowing disease progression rather than simply managing symptoms.

The Role of Arc in Alzheimer’s Disease Progression

Recent research published in Cell reveals that a common brain protein, Arc—which normally helps neurons communicate with one another—may be inadvertently helping the disease spread. Researchers discovered that Arc may act like a delivery vehicle for toxic Tau, carrying it out of damaged brain cells and into healthy ones. As Tau damage reaches additional brain regions, more neurons are harmed, symptoms intensify, and the disease can eventually become fatal.

Jason Shepherd, professor of neurobiology at University of Utah Health and senior author on the study, stated, I’m excited by the fact that we’ve identified a new way of potentially stopping the progression of Alzheimer’s disease. In experiments involving mice, researchers found that Arc helps spread Tau from sick brain cells to healthy ones. The study suggests that Tau export from sick cells may keep them alive longer, even as the protein spreads the disease to new brain regions. If therapies could be designed to target the spread, they could be a powerful tool to stop Alzheimer’s disease from getting worse.

Mechanisms of Spread in Parkinson’s Disease

While Alzheimer’s research focuses on Arc, scientists at the Yale School of Medicine (YSM) have identified two proteins on the surface of neurons that may help drive the spread of Parkinson’s disease in the brain. Parkinson’s is a progressive neurological disorder in which neurons gradually deteriorate and die, and it is a growing health concern in the United States. The Parkinson’s Foundation estimates that approximately 1.1 million Americans are living with the disease, with nearly 90,000 people diagnosed each year.

A key feature of Parkinson’s is the buildup of a misfolded protein called α-synuclein. As this toxic protein moves from one neuron to another, it contributes to the worsening of symptoms over time, including tremors, trouble with balance, and slowed movement. The findings, published in the journal Nature Communications, suggest that two proteins on the surface of nerve cells act as entry points for this toxic protein. By determining how α-synuclein enters healthy neurons, researchers hope to open the door to treatments designed to slow or even stop the disease instead of only managing its symptoms.

In experiments involving laboratory and animal models, blocking those proteins dramatically reduced disease-related damage.

Future Therapeutic Directions

The identification of these proteins provides a potential roadmap for future disease-modifying therapies. By understanding the molecular mechanism of how proteins like Tau and α-synuclein spread, scientists are shifting their strategy from trying to eliminate the proteins entirely to preventing them from reaching healthy brain cells.

Technion researchers have also noted that the brain’s protein-disposal system can sometimes inadvertently contribute to this spread; instead of destroying toxic proteins, cells sometimes expel them to neighboring tissues, potentially accelerating disease progression. Because these studies were primarily conducted in mice, the researchers emphasize that further investigation is required. However, the discovery of these transport mechanisms presents a significant advancement in understanding neurodegeneration, shifting the focus toward intercepting the movement of toxic proteins between cells.