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DNA ‘spelling mistakes’ may cause dementia

LONDON: Many cases of dementia may arise from spontaneous errors in our DNA that arise as cells divide and reproduce, according to a study published Monday.

DNA ‘spelling mistakes’ may cause dementia

Only a small proportion of cases of dementia are thought to be inherited. iStock



LONDON: Many cases of dementia may arise from spontaneous errors in our DNA that arise as cells divide and reproduce, according to a study published Monday.

Only a small proportion of cases of dementia are thought to be inherited—the cause of the vast majority is unknown, said researchers at the University of Cambridge in the UK.

The study, published in the journal Nature Communications, suggests that for many people with neurodegenerative diseases such as Alzheimer’s and Parkinson’s, the roots of their condition trace back to their time as an embryo developing in the womb.

In common neurodegenerative diseases, toxic proteins build up in the brain, destroying brain cells and damaging brain regions, leading to symptoms including personality changes, memory loss and loss of control.

Only around one in twenty patients has a family history, where genetic variants inherited from one or both parents contributes to disease risk, researchers said.

The cause of the majority of cases—which are thought to affect as many as one in ten people in the developed world—has remained a mystery, they said.

Researchers hypothesised that clusters of brain cells containing spontaneous genetic errors could lead to the production of misfolded proteins with the potential to spread throughout the brain, eventually leading to neurodegenerative disease.

“As the global population ages, we’re seeing increasing numbers of people affected by diseases such as Alzheimer’s, yet we still don’t understand enough about the majority of these cases,” said Professor Patrick Chinnery from the University of Cambridge.

The researchers examined 173 tissue samples from from 54 individual brains: 14 healthy individuals, 20 patients with Alzheimer’s and 20 patients with Lewy body dementia.

The team used a new technique that allowed them to sequence 102 genes in the brain cells over 5,000 times.

These included genes known to cause or predispose to common neurodegenerative diseases.

The study found ‘somatic mutations’ — spontaneous, rather than inherited, errors in DNA — in 27 out of the 54 brains, including both healthy and diseased brains.

Together, these findings suggest that the mutations would have arisen during the developmental phase—when the brain is still growing and changing—and the embryo is growing in the womb.

Combining their results with mathematical modelling, their findings suggest that ‘islands’ of brain cells containing these potentially important mutations are likely to be common in the general population.

“These spelling errors arise in our DNA as cells divide, and could explain why so many people develop diseases such as dementia when the individual has no family history,” said Chinnery.

“These mutations likely form when our brain develops before birth—in other words, they are there waiting to cause problems when we are older,” he said.

“Our discovery may also explain why no two cases of Alzheimer’s or Parkinson’s are the same. Errors in the DNA in different patterns of brain cells may manifest as subtly different symptoms,” said Chinnery. PTI

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