Cell-free DNA circulating in the blood can indicate early signs of dementia and frailty

Cell-free DNA circulating in the blood can indicate early signs of dementia and frailty

In a long-term prospective study of more than 600 elderly participants, researchers at Johns Hopkins Medicine say they have evidence that higher levels of cell-free DNA circulating in the blood may signal an increased risk of chronic inflammation, which is associated with early signs of frailty and dementia.

The findings, published Oct. 11 in the Journal of Alzheimer's Disease, could advance the search for relatively simple blood tests that detect the risk of Alzheimer's disease and other forms of cognitive decline.

Circulating cell-free genomic DNA (ccf-gDNA) is a long-known product of natural cell death in the body. When cells die through apoptosis (programmed cell death), the cells shrink, break down their plasma membrane, and eventually rupture, releasing their contents, including DNA fragments, into the body. These fragments enter the bloodstream as outdoor DNA.

These ccf gDNA fragments can trigger long-term chronic inflammatory responses, which have previously been linked to the premature destruction and aging of tissues and organs, including the brain. The body sees these ccf gDNA fragments as something that needs to be removed, which is why the body's immune system works faster than it should. Such an overload of the immune system may be a factor in detecting the onset of dementia.”

Peter Abadir, MD, Associate Professor of Geriatric Medicine and Gerontology, Johns Hopkins University School of Medicine

For the new study, researchers examined the blood of 631 people with an average age of 79 who had no cognitive impairments at the start of the study. Participants received annual physical and cognitive testing at the time of each blood draw. The researchers found that higher levels of ccf-gDNA in the blood were associated with greater cognitive decline and worsening frailty over the eight-year study period.

According to the Alzheimer's Association, Alzheimer's disease affects an estimated 6.5 million people in the United States, and there are no known cures or effective therapies. However, the potential of a blood test to identify those most at risk or in early stages could lead to supportive services and other interventions to plan for, compensate for, or slow worsening of symptoms.

"Our global population is aging rapidly. We have made so many advances that have helped extend our lifespan, so the goal now is to live healthier lives as we age," says Dr. Lolita Nidadavolu, assistant professor of geriatrics and gerontology at Johns Hopkins University School of Medicine. "Dementia and frailty are becoming increasingly common. Many people know someone affected by these conditions. With a single blood draw, we may be able to identify people who can benefit from early interventions."

In the future, the researchers hope to learn more about the cellular origin of ccf gDNA fragments. If researchers can determine that a large amount of these fragments come from a specific cell type, the hope is that they can advance the search for drugs that target the aging and dementia processes.

Other scientists who contributed to this research include Danielle Feger, Yuqiong Wu, Alden Gross, Jeremy Walston and Esther Oh from Johns Hopkins and David Bennett and Francine Grodstein from Rush University.

Source:

Johns Hopkins Medicine

Reference:

Nidadavolu, L.S., et al. (2022) Circulating cell-free genomic DNA is associated with increased risk of dementia and alteration in cognitive and physical function. Journal of Alzheimer's Disease. doi.org/10.3233/JAD-220301.

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