Study: Non-inherited dementia linked to DNA 'spelling mistakes'

Oct. 15 (UPI) — Non-inherited forms of dementia likely develop because of spontaneous “spelling mistakes” in DNA that arise as cells divide and reproduce, according to a study.

Researchers at the University of Cambridge believe most people with neurodegenerative diseases such as Alzheimer’s disease and Parkinson‘s disease can trace their condition to when their embryos were developing in the womb. The findings were published Monday in the journal Nature Communications.

“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,” Dr. Patrick Chinnery, a researcher in the Medical Research Council’s Mitochondrial Biology Unit and the Department of Clinical Neurosciences at the University of Cambridge, said in a press release. “Why do some people get these diseases while others don’t? We know genetics plays a part, but why do people with no family history develop the disease?”

Only 1 percent of dementia cases are passed on to children and grandchildren, according to the Alzheimer’s Society. But this probability depends on the type, with 30 percent to 50 percent of frontotemporal dementias, including Lou Gehrig‘s disease, inherited. Huntington’s disease is also usually inherited because it involves only one faulty copy of the gene to be inherited.

Scientists have been trying to find the roots of dementia.

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

In addition, he said it explains 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,” he said.

Researchers examined 173 tissue samples from the Newcastle Brain Tissue Resource, which is part of the MRC’s UK Brain Banks Network. In all, 611,000 cells were studied, including ones that were mutated.

The samples were taken from 14 healthy individuals, 20 patients with Alzheimer’s and 20 patients with Lewy body dementia, which is a common type of dementia.

Using a new technique, they sequenced 102 genes in the brain cells over 5,000 times that are known to cause or predispose to common neurodegenerative diseases.

Spontaneous mutations, rather than inherited errors in DNA, occurred in 27 out of the 54 brains, including healthy and diseased brains.

By combining the sample results with mathematical modelling, researchers believe that “islands” of brain cells containing these potentially important mutations likely are frequently found in the general population.

Chinner said it’s possible the research could help with new treatments for rare genetic forms of neurodegenerative diseases, and specifically for people with non-inherited forms — which could also help people with more common forms of the disease.

“The question is: how relevant are these treatments going to be for the ‘common-or-garden’ variety without a family history?” Chinner said. “Our data suggests the same genetic mechanisms could be responsible in non-inherited forms of these diseases, so these patients may benefit from the treatments being developed for the rare genetic forms.”

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