Scientists may have finally found how Alzheimer's spreads through the brain
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Alzheimer's disease is marked by the buildup of a toxic protein called Tau, which damages and eventually kills brain cells.
As this harmful protein moves into new areas of the brain, the disease progresses, leading to worsening memory loss and cognitive decline. Now, researchers have uncovered an unexpected player in that process. In a study of mice, they found that a brain protein called Arc, which normally helps neurons communicate, also appears to help toxic Tau spread from diseased brain cells to healthy ones.
The discovery points to a possible new strategy for slowing Alzheimer's disease. Rather than trying to eliminate Tau entirely, future treatments might stop it from reaching healthy brain cells in the first place. "I'm excited by the fact that we've identified a new way of potentially stopping the progression of Alzheimer's disease," says Jason Shepherd, PhD, professor of neurobiology at University of Utah Health and senior author of the study.
To investigate how Alzheimer's spreads, the researchers compared mouse models of the disease with and without the Arc protein. Their experiments showed that Arc is essential for moving toxic Tau between neurons. Under normal conditions, Arc plays an important role in brain function.
The protein packages itself inside tiny membrane bound sacs known as extracellular vesicles (EVs), which travel from one neuron to another carrying important cellular signals. The researchers found that toxic Tau can exploit this natural communication system. By attaching itself to Arc inside these microscopic vesicles, Tau is able to travel from an unhealthy neuron into a healthy one, where it can continue spreading disease.
Every neuron contains Tau, but in Alzheimer's disease the protein begins clumping into large, sticky tangles that interfere with the cell's internal transport system before eventually killing the neuron. Mitali Tyagi, PhD, postdoctoral research associate at Washington University in St. Louis and first author of the study, who conducted the research while a neuroscience graduate student in the Shepherd Lab at U of U Health, compares these tangles to "glue monsters."
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