Scientists Discover How Sugars Control Hallmark Alzheimer’s Protein

A study by scientists in Canada and the US has shown that a chemical change to a hallmark Alzheimer’s protein, tau, can stop it from forming toxic tangles – a characteristic of the disease. The findings, published online on 26 February in the journal Nature Chemical Biology, open up new avenues for research into treatments to slow the progression of the disease.

A defining feature of Alzheimer’s is the over activation of a protein called tau – causing it to form toxic tangles inside nerve cells. The researchers found that adding a sugar molecule called O-GlcNAc to tau could prevent it from sticking together.

The scientists tested the approach using mice which have high levels of a sticky form of tau. In these mice, tau builds up over time – killing nerve cells and causing movement and behaviour problems. These mice were treated for 36 weeks with a drug which increases the amount of O-GlcNAc on tau and researchers found that the mice had fewer tau tangles in the brain, including the parts of the brain involved in thinking and memory. While tau in these mice was still over activated, O-GlcNAc appeared to block the next step of tangle formation.

Problems with sugar metabolism have been seen in brain cells in the early stages of Alzheimer’s and the researchers suggest this may limit the amount of O-GlcNAc available to protect tau – driving the formation of toxic tangles.

Dr Marie Janson of Alzheimer’s Research UK, said:
“We know that the toxic build up of tau is a key feature in Alzheimer’s and other dementias, but what is still unclear is exactly what causes it and how it can be stopped. This study provides some answers and encouragingly shows that small changes to tau can have a real effect on how it behaves inside cells.

“Understanding more about how hallmark proteins involved in Alzheimer’s are controlled at a molecular level will provide clues for disease prevention and help us develop ways of tackling this devastating disease. Over 820,000 people in the UK live with dementia, so the need for more research has never been greater.”

This material has been published with the kind permission of Alzheimer Research UK.

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