While recent access to DNA reports like 23andMe has stoked fear amongst those who received confirmation that they carry one or two copies of the ApoE4 gene, which can increase your chances of developing Alzheimer’s up to twelve times, researchers say only 5 percent of dementia cases are tied to genes. The other 95 percent, according to a new study, might stem from spontaneous errors in DNA that happen in the womb.
“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 Patrick Chinnery, a neuroscientist at the University of Cambridge. He asked the question everyone who has encountered dementia wants to know the answer to: “Why do some people get these diseases while others don’t?” asked Chinnery. “We know genetics plays a part, but why do people with no family history develop the disease?”
Chinnery and his colleagues set out to answer that question by looking at 173 tissue samples from 54 different people: 14 healthy individuals, 20 patients with Alzheimer’s and 20 patients with Lewy body dementia. They sequenced the DNA using a special technique called ultra high-depth re-sequencing. When they looked at the results, they were able to see that spontaneous errors occurred in 27 of the 54 people, both in healthy brains and those with dementia. Researchers working on this study referred to them as ‘spelling errors’—mistakes in cell division that happen as a fetus develops in the womb.
“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 sat there waiting to cause problems when we are older.”
The researchers said the errors sit like ‘islands’ within the brain, eventually jumpstarting the formation of toxic proteins like beta-amyloid and tau—a common start to most neurodegenerative diseases. Over time, proteins that seeded from this island spread throughout the brain, according to the theory of the study.
Chinnery said the evidence could offer a reason why Alzheimer’s and other types of dementias present differently in different people. Some people experience aggression and extreme changes in personality, while others do not. Some cases of Alzheimer’s develop quickly; others may stretch out over a decade.
“Our discovery may also explain why no two cases of Alzheimer’s or Parkinson’s are the same,” said Chinnery. “Errors in the DNA in different patterns of brain cells may manifest as subtly different symptoms.”
However, more research is needed before concluding that most dementias start in the womb. Scientists did not find DNA errors in all of the dementia brains that were studied, though that could be due to the small area of the brain that was sampled.
“The small errors that can occur as brains develop are often harmless, but can sometimes lead to conditions such as cancer or dementia,” said James Pickett, of the Alzheimer’s Society. “It’s interesting to see that many of the mutations in this study were found in the area of the brain that Alzheimer’s starts in. It highlights an important area of research to consider, however because this is such a small study we can’t jump to conclusions yet.”
This study was published in the journal Nature Communications.