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The Making of Medicine

Toxic Tau’s Toll on the Brain

Our George Bloom, PhD, and colleagues have discovered a dire effect that tau protein can have on our brain cells, and that finding could pave the way for new treatments for Alzheimer's disease and other "tauopathies."

Tau has long been suspected as a contributor to Alzheimer's, but there has been precious little concrete evidence of how it affects our neurons, the fundamental units of our brains. Professor Bloom and his team found that tau warps the shape of the nuclei of neurons, causing them to "invaginate," or fold in on themselves. This disrupts the function of the genetic material contained within and causes the cells the begin producing more tau.

And that may explain, at least in part, how tau spreads through our brains.

“Our discovery that tau oligomers alter the shape of the nucleus drove us to the next step – testing the idea that changes in gene expression are caused by the nuclear shape change,” Professor Bloom told me. “That’s exactly what we saw for many genes, and the biggest change is that the gene for tau itself increases its expression almost three-fold. So bad tau might cause more bad tau to be made by neurons – that would be like a snowball rolling downhill.”

The researchers found that patients with Alzheimer’s had double the number of invaginated nuclei as people without Alzheimer's. Additional research into how this process happens could open the door to new ways to prevent and treat Alzheimer’s and other tauopathies.

“The toxic tau described here is actually released from neurons, so if we can figure out how to intercept it when it’s floating around in the brain outside of neurons, using antibodies or other drugs, it might be possible to slow or halt progression of Alzheimer’s disease and other tauopathies,” Professor Bloom said.

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