Research from the University of Utah uncovered one way a toxic protein linked to Alzheimer’s disease may spread from sick brain cells to healthy ones. The findings could eventually help researchers develop new approaches to slow the progression of the disease.
“Alzheimer’s disease is the most common form of dementia in older adults," said Jason Shepherd, a professor of neurobiology at the University of Utah.
Alzheimer’s is a progressive disease in which brain cells become damaged and eventually die, leading to worsening memory loss and cognitive decline.
The disease is associated with abnormal buildups of two proteins in the brain. They are beta-amyloid, which forms plaques outside of neurons, and tau, which forms tangles inside them. As Alzheimer’s progresses, toxic forms of tau spread through the brain, damaging more cells along the way.
But exactly how a protein trapped inside one brain cell moves into another cell has remained an important question.
Shepherd and an international team of researchers recently identified one possible answer. It involves ARC, which is a protein that normally plays an important role in forming memories. It stands for activity-regulated cytoskeleton-associated protein. It can also package material from inside a cell into tiny membrane-bound containers called extracellular vesicles. And they kind of look like tiny balloons.
“We found that this ARC protein can hijack tau, bring it into this balloon, and get rid of it from the cell," Shepherd said.
This means that after packaging tau inside the tiny balloons, the neuron would normally remove the toxic protein from the cell. The problem is that other cells can then pick them up.
“The consequence of that is this balloon can then get taken up by other surrounding cells, and that toxic protein can eventually get transported to healthy cells, so it’s a double-edged sword,” Shepherd said.
The researchers found that genetically removing ARC from mice dramatically reduced the spread of tau between brain cells. But without ARC to help remove tau from neurons, more of the protein accumulated inside individual cells, where it was associated with increased cell damage early in the disease.
That means the process could potentially offer researchers a new target for slowing the progression of Alzheimer’s. But Shepherd cautions that the research is still at an early stage.
Even though researchers conducted much of the work using cells and mouse models, they also found similar interactions between the proteins in brain tissue from people with Alzheimer’s.
Shepherd says the discovery grew out of basic research on how ARC normally functions in memory, rather than a direct search for an Alzheimer’s treatment.
“We never know when a breakthrough is going to be made in a disease, but 99% of the time it’s because some other lab has done the basic groundwork,” Shepherd said.
The scientific journal “Cell” published the study.
