New Research May Totally Turn Our Understanding of Dementia on Its Head

Person putting together puzzle of head with one missing piece in middle

Most researchers believe that only a small percentage of dementias are inherited. Only about one in 20 are believed to be inherited. Researchers at the University of Cambridge published research in the journal Nature Communications that suggests spontaneous DNA mutations may cause the majority of dementias.

“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, from the Medical Research Council (MRC) Mitochondrial Biology Unit and the Department of Clinical Neurosciences at the University of Cambridge, who led the research. “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?”

The research team studied 173 tissue samples from the Newcastle Brain Tissue Resource, part of the Medical Research Council (MRC)’s UK Brain Banks Network. The samples were from 54 people, 14 healthy, 20 with Alzheimer’s, 20 with Lewy body dementia. They sequenced 102 genes in brain cells over 5,000 times, including genes linked to common neurodegenerative diseases. They found spontaneous (somatic mutations) in 27 out of the 54 brains, including both healthy and diseased.

“These spelling errors arise in our DNA as cells divide and could explain why so many people develop disease such as dementia when the individual has no family history,” stated Chinnery. “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. Errors in the DNA in different patterns of brain cells may manifest as subtly different symptoms.”

Part of the researchers’ theory is that “islands” of brain cells hold the mutations and are, in fact, common in the general population. Additional research will need to be conducted to determine if the mutations are more common in dementia patients than in healthy patients.

The research didn’t find the mutations in all brain samples from dementia patients. They speculate that this isn’t necessarily their absence, but because they only sample small areas of each brain region. Nor did they analyze for the mutations in Parkinson’s patients.

This research has the potential to help physicians more closely diagnose varying types of Alzheimer’s and dementias, if biomarkers and resultant assays can be identified and developed.

Ellen Kuhl, a professor of medical engineering at Stanford University, also developed a computer simulation that tracks the spread of defective proteins in the brain. The proteins are linked to a number of neurodegenerative diseases, including Alzheimer’s, Parkinson’s, and ALS.

The work was presented in Stanford News. “We hope the ability to model neurodegenerative disorders will inspire better diagnostic tests and, ultimately, treatments to slow down their effects,” Kuhl stated. The work was published in the journal Physical Review Letters.

All three diseases are marked by clumps of misfolded proteins that accumulate in the brain. Kuhl and her team studied brain slices acquired from patients who died after developing one of the diseases. Earlier researchers had stained the brain samples to identify various proteins.

Kuhl’s group created mathematical models that simulated the pattern of defective proteins and how they spread throughout the brain, in some cases, over 30-year periods. “Imagine a domino effect,” Kuhl stated. She is part of the Stanford Neurosciences Institute and Stanford Bio-X. “What our model does is connect the dots between the static data points, mathematically, to show disease progression in unprecedented detail.”

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