Alzheimer’s breakthrough as scientists find toxic protein spread in brain through extracellular space

US scientists at the Columbia University Medical Center have discovered that a toxic Alzheimer’s protein spreads inside the brain through the extracellular space that surrounds the brain's neurons. The protein spreads by jumping from one neuron to the other.

The spread of the toxic protein, tau, could help scientists know why in the early stages of the disease, only one portion of the brain gets affected, while in later stages, multiple areas are affected. The researchers may be able to stop the protein from spreading one neuron to the other by learning how tau spreads.

The study, published in the journal Nature Neuroscience, says that knowing how tau protein spreads could stop the spread of Alzheimer’s disease to other areas of the brain, which leads to a more severe form of dementia.

The very idea that Alzheimer’s can spread through one’s brain gained importance a few years ago when Duff and other Columbia researchers discovered that tau spread from neuron to neuron through the brains of mice.

“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,” Karen Duff, PhD, professor in the department of pathology and cell biology in the Taub Institute for Research on Alzheimer's Disease and the Aging Brain and professor of psychiatry at New York State Psychiatric Institute, said in a statement.

Lead scientist Jessica Wu, PhD, a former post-doctoral researcher at the Taub Institute who is currently at Massachusetts Institute of Technology, tracked the movement of tau from one neuron to another and discovered how tau travels.

Wu said that neurons may release toxic tau protein into extracellular space. These get picked by other neurons and help in the spread. Tau can affect other regions of the brain as it can travel long distances within the neuron before its release.

The study also revealed that tau spread accelerates when neurons are more active. Gustavo Rodriguez, PhD, and Abid Hussaini, PhD, showed acceleration of tau spread and more neurodegeneration in brains of mice by stimulating activity of neurons.

Duff suggested “that clinical trials testing treatments that increase brain activity, such as deep brain stimulation, should be monitored carefully in people with neurodegenerative diseases.”

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