Alzheimer’s disease is the most common cause of dementia and affects millions of people worldwide. It slowly destroys memory, thinking, and the ability to carry out everyday tasks.
As the disease progresses, brain cells die and different parts of the brain gradually stop working. Although current medicines may temporarily improve symptoms for some people, none can stop the disease from getting worse.
Scientists have known for many years that two proteins, amyloid and Tau, play important roles in Alzheimer’s disease. Tau normally helps support the internal structure of nerve cells.
However, in Alzheimer’s disease it changes shape and forms sticky clumps inside neurons. These clumps eventually damage and kill the cells. Even more concerning, small pieces of abnormal Tau can spread from one brain cell to another, allowing the disease to move through the brain over time.
Researchers at University of Utah Health have now identified a protein that appears to help this spread happen. Their findings, published in the journal Cell, may point to a completely new treatment strategy.
The protein is called Arc. Under normal conditions, Arc performs an important job in healthy brains by helping neurons communicate during learning and memory. Arc travels between brain cells inside tiny membrane-covered bubbles called extracellular vesicles. These microscopic packages normally carry useful biological messages.
The research team discovered that toxic Tau can attach itself to Arc and hide inside these tiny vesicles. In effect, Tau uses Arc as transportation to move from damaged neurons into healthy ones. Once inside a healthy neuron, the abnormal Tau acts like a template, causing healthy Tau proteins to become abnormal as well. New clumps form, and the destructive cycle continues.
Using mouse models of Alzheimer’s disease, the researchers found that extracellular vesicles contained both Arc and Tau. These vesicles were capable of spreading Tau to healthy brain cells. However, when the scientists removed Arc, almost no Tau was transferred to other neurons, dramatically reducing the spread of disease.
The findings also revealed that Arc has a complicated role. Removing Arc slowed the spread of Tau, but it also caused damaged neurons to accumulate larger amounts of toxic Tau inside themselves. Those neurons died more quickly because they could no longer remove some of the harmful protein.
This means simply blocking Arc may not be the best treatment. Instead, researchers believe future therapies could focus on stopping Tau-containing vesicles after they leave diseased cells but before they reach healthy ones. Such an approach might allow sick neurons to remove harmful Tau while preventing the disease from spreading further.
The scientists also examined human brain tissue and found evidence that Arc and Tau travel together in similar extracellular vesicles, suggesting the same process may occur in people. However, much more research will be needed before any new treatment can be tested in patients.
The discovery opens an exciting area of Alzheimer’s research because slowing disease spread could help preserve memory and thinking for longer. Even if existing brain damage cannot be reversed, preventing additional neurons from becoming infected may slow future decline.
The research was published in Cell.
One of the greatest strengths of this study is that it identifies a detailed biological mechanism explaining how Tau may spread between neurons. Rather than simply observing disease progression, the researchers uncovered a possible transport system that could become a treatment target.
However, the work was mainly performed in mice, so scientists cannot yet assume the same results will occur in humans. Larger studies are needed before clinical trials begin. Even so, this discovery represents an important step toward therapies designed to slow Alzheimer’s progression rather than simply treating symptoms.
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Source: University of Utah Health.
