New research reveals at least one way that the toxic tau protein associated with Alzheimer’s disease jumps from brain cell to brain cell – it spreads through the extracellular space that surrounds them.

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The team found tau protein can spread via extracellular space. In this image, orange shows where it has traveled from one neuron to another.
Image credit: Laboratory of Karen Duff Ph.D.

In the brain there is a protein called tau, which normally helps maintain the straight tracks that carry vital nutrients and other materials inside neurons or brain cells.

When the tau protein malfunctions, it collapses into twisted strands or tangles, disrupting the transport tracks and eventually causing the death of the cell.

This toxic version of tau is one of the hallmarks of Alzheimer’s disease, an irreversible, progressive brain disorder that slowly destroys memory and ability to think and reason, eroding people’s capacity to lead independent lives.

Another hallmark of Alzheimer’s disease is plaques of another protein called beta-amyloid. Plaques and tau tangles tend to spread through the brain in a predictable pattern as Alzheimer’s disease progresses.

The new research, led by Columbia University Medical Center (CUMC), New York, NY, and published in the journal Nature Neuroscience, suggests one way that tau protein jumps from neuron to neuron is via the extracellular space.

Senior and corresponding author Karen Duff, professor of pathology and cell biology at CUMC, says:

“By learning how tau spreads, we may be able to stop it from jumping from neuron to neuron. This would prevent the disease from spreading to other regions of the brain, which is associated with more severe dementia.”

In earlier work, Prof. Duff and colleagues found that tau spreads from neuron to neuron in the brains of mice.

In the new study, the researchers take a closer look at what happens to tau.

Fast facts about Alzheimer’s
  • Alzheimer’s is the most common cause of dementia in older adults
  • It currently ranks as the sixth leading cause of death in the United States
  • The brain damage seen in Alzheimer’s disease may start 10 years or more before problems with memory and thinking appear.

Learn more about Alzheimer’s

They tracked the movement of the protein as it traveled from one nerve cell to another in mice.

They found that the neurons secrete the protein into extracellular space – the fluid-filled medium between the cells – where it is then picked up by neighboring cells.

Neurons can be quite long, and the protein can travel a long way inside the cell before its release, which could explain why the faulty protein is able to infect another part of the brain.

Using techniques called “optogenetic and chemogenetics,” the team also found that increased activity in the neuron stimulates the release of tau and leads to more neurodegeneration.

The researchers say more work is now needed to establish whether these findings are true of humans as well.

However, in the meantime, they call for careful monitoring of trials of deep brain stimulation and other ways of enhancing brain activity in people with neurodegenerative diseases.

This finding has important clinical implications. When tau is released into the extracellular space, it would be much easier to target the protein with therapeutic agents, such as antibodies, than if it had remained in the neuron.”

Prof. Karen Duff

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