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Health

Alzheimer’s disease study reveals how toxic clumps deform neurons at their core: ScienceAlert

It’s not fully understood how Alzheimer’s disease appears or takes hold, but tangled tau proteins in the brain are thought to play a key role — and new research is shedding light on the devastating damage these protein tangles can cause .

The more we know about how these proteins work in Alzheimer’s-affected brains, the better we can target efforts to find effective treatment for the disease and other tauopathies (neurodegenerative disorders caused by tangles of tau ).

A team from the University of Virginia closely examined brain tissue from people who died with Alzheimer’s disease, as well as brain tissue from mice bred to develop a similar disease, to identify the effects of tau proteins.

“A lot of fantastic research has been done by other labs to understand how toxic tau spreads from neuron to neuron in the brain, but very little is known about exactly how toxic tau damages neurons, and this question is the motivation for our new paper,” explains biologist George Bloom.

Researchers found that tau oligomers – protein clumps smaller than the tangles that eventually grow – damage the structure of nuclei inside neurons, causing them to fold in on themselves.

This is then likely to modify genetic processing in neurons, according to the team behind the study. Although this type of nuclear breakdown has previously been associated with Alzheimer’s disease, its cause was not yet clearly established.

“Our discovery that tau oligomers change the shape of the nucleus led us to the next step: testing the idea that changes in gene expression are caused by changing nuclear shape,” says Bloom.

“This is exactly what we observed for many genes, and the most important change is that the tau gene itself increases its expression threefold. So bad tau could cause more bad tau to be produced by the neurons – it would be like a snowball rolling down.”

The next step is to study the precise biological mechanisms by which tau oligomers trigger this damage and thus disrupt the normal functioning of brain cells and the brain as a whole.

In a way, tau oligomers are precursors to tau proteins, suggesting that stopping this type of protein buildup could also stop Alzheimer’s disease — but we’ll need a lot more research before that. to get there.

“The toxic tau described here is actually released by neurons, so if we can figure out how to intercept it as it floats around the brain outside of neurons, using antibodies or other drugs, it might be possible to slow or stop the progression of Alzheimer’s disease and other tauopathies,” says Bloom.

The research was published in Alzheimer’s and dementia.

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