Many Cases of Dementia Could Be Influenced By DNA Errors

The development of dementia in cases that are not inherited may be influenced by errors in our DNA that occur when cells divide and replicate, according to a paper published in the journal Nature Communications.

Dementia is a broad term used to describe several neurodegenerative disorders. Only 5 percent of cases are thought to be driven by rare inherited mutations in the genetic code which are passed down from one or both parents. The causes of the vast majority of cases, however, in which there is no family history, remains a mystery.

Scientists know that common types of dementia, such as Alzheimer's and Parkinson's, are characterized by a buildup of toxic proteins in the brain, which destroy brain cells and damage brain regions, leading to symptoms that include personality changes, memory loss and reductions in motor function.

Now, a team led by researchers from the University of Cambridge, have suggested that clusters of brain cells containing spontaneous genetic errors may lead to the production of these toxic proteins, which could potentially spread through the brain.

"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," Patrick Chinnery, from the Medical Research Council Mitochondrial Biology Unit and the Department of Clinical Neurosciences at Cambridge, said in a statement.

"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?" he said.

For their research, the scientists examined 173 tissue samples from 54 individuals stored in the U.K. Brain Banks network. Fourteen of these individuals were healthy, 20 had Alzheimer's and another 20 had a common type of dementia known as Lewy body disease.

The team then used an advanced technique to sequence 102 genes in the tissue samples more than 5,000 times. These genes include those that are known to cause or predispose people to common neurodegenerative diseases.This approach revealed "somatic mutations"—errors that occur spontaneously in DNA rather than being inherited—in 27 out of the 54 brain tissue samples, from both healthy and diseased brains.

These findings suggest that the mutations occurred during the developmental phase when the embryo was growing in the womb.

"We found that half of the brains we studied contained somatic mutations, likely to have occurred during brain development," Chinnery told Newsweek. "Using a [mathematical] model, we made predictions about how frequent the mutations are in all of us. Our predictions suggest that we all contain patches of brain cells containing mutations [alterations in the genetic code] and that these will sometimes affect the genetic code known to cause diseases like Alzheimer's."

"These 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."

"Our discovery may also explain why no two cases of Alzheimer's or Parkinson's are the same," he said. "Errors in the DNA in different patterns of brain cells may manifest as subtly different symptoms."

Currently, it is too early to say whether the findings of the study could help in the diagnosis and treatment of dementia. However, the researchers believe the results may validate the approach of pharmaceutical companies that are trying to develop new treatments for the rarer, genetically inherited types of neurodegenerative diseases.

"The question is: How relevant are these treatments going to be for the common-or-garden variety without a family history?" Chinnery said. "Our data suggest the same genetic mechanisms could be responsible in noninherited forms of these diseases, so these patients may benefit from the treatments being developed for the rare genetic forms."

According to Chinnery, more research is needed to determine whether the mutations are more common in patients with dementia and, thus, confirm if they are actually contributing to its development.

David Reynolds, chief scientific officer at Alzheimer's Research U.K., who was not involved in the latest research, praised the quality of the study but warned that the results should be viewed with caution for now.

"We know the development of dementia is influenced by a complex mix of age, genetics and lifestyle factors," he told Newsweek. "Our genetic makeup can have a huge impact on our health, and errors in this DNA code can occur in embryonic development as well as throughout our lives."

"This well-conducted research using state-of-the-art DNA sequencing technology allowed scientists to look closer than ever at the genetic differences between cells in the brain, he said. "Although the researchers found DNA errors in genes associated with neurodegenerative diseases, the study was not sufficiently large enough to reveal if or how these errors might directly contribute to the development of a disease like Alzheimer's."

He explained that in recent decades, genetic clues have been crucial for uncovering new areas of biology to explore in the search for treatments for diseases like Alzheimer's.

"This study provides a valuable platform for further research to continue to unravel the complex role our genes play in the development of the diseases that cause dementia," Reynolds said.

This article has been updated to include additional comments from Patrick Chinnery.