Scientists in Japan have identified metabolic compounds in the blood that are linked to dementia.
The study found that the levels of 33 metabolites in patients with dementia were different from those in the elderly with no existing health problems. Their results, published in PNAS this week, could one day help diagnose and treat dementia.
“Metabolites are chemical substances that are produced by vital chemical reactions that take place in cells and tissues,” said first author Dr. Takayuki Teruya, who works in the G0 cell division of the Okinawa Institute of Science and Technology Graduate University (OIST). “Our bodies normally keep these levels in balance, but as we get older and develop diseases like dementia, these levels can fluctuate and change.”
Dementia is not just a single disease, but a general term used to describe a range of symptoms, including a slow but typically irreversible decline in the ability to remember, think, make decisions, or carry out everyday activities . Of all age-related diseases, dementia is one of the most serious, not just for patients and their families, but for society as a whole, with an estimated 55 million people worldwide with the disease.
While scientists know that dementia is caused by nerve damage, the exact cause of this damage and methods of detecting and treating it remain unclear.
In the study, the research team analyzed blood samples from eight dementia patients and eight healthy elderly people. They also collected samples from eight healthy young people to use as reference. Unlike most studies that analyzed blood metabolites, this research included compounds found in red blood cells.
“Blood cells are difficult to handle because they experience metabolic changes if left untreated, even for a short time,” explains Dr. Teruya.
However, the research team recently developed a way to stabilize metabolites in red blood cells, which for the first time can study the link between red blood cell activity and dementia.
The scientists measured the levels of 124 different metabolites in whole blood and found that 33 metabolites, divided into 5 different subgroups, correlated with dementia. Seven of these compounds increased in dementia patients, while 26 of these compounds showed decreases in levels. Twenty of these compounds, including nine that were abundant in red blood cells, had not previously been linked to dementia.
“Identifying these compounds means we are one step closer to the molecular diagnosis of dementia,” said Professor Mitsuhiro Yanagida, lead author of the study who heads the G0 Cell Unit at OIST.
The seven metabolites that showed elevated levels in patients with dementia were found in blood plasma and belonged to subgroup A of the metabolites. Importantly, some of these compounds are believed to have toxic effects on the central nervous system.
It’s too early to say, but it could point to a possible mechanistic cause of dementia, as these connections can lead to brain impairment. “
Professor Mitsuhiro Yanagida, senior author
The research team plans to test this idea in the next steps of their research by seeing if an increase in these metabolites can trigger dementia in animal models such as mice.
The remaining 26 compounds that decreased in dementia patients compared to healthy elderly people belonged to four other metabolite subgroups, BE.
Six metabolites that decreased in dementia patients were classified into subgroup B based on their similar structure. These metabolic compounds are antioxidants that protect cells and tissues by reducing damage from free radicals – unstable molecules created by chemical reactions in cells. The researchers found that these food-derived antioxidant compounds are very abundant in the red blood cells of healthy elderly people.
“It could be that red blood cells not only provide oxygen, but also important metabolic products that protect the nervous system from damage,” said Dr. Teruya.
The remaining subgroups contain compounds that researchers believe play roles in nutritional supply, maintaining energy reserves, and protecting neurons from damage.
“We hope to be able to start some intervention studies in the future, either by supplementing dementia patients with metabolic compounds of the subgroup BE or by inhibiting the neurotoxins of the subgroup A, to see if this can be slowed down, prevented or even reversed symptoms of one Dementia, “said Prof. Yanagida.
The research was carried out by the Okinawa Institute of Science and Technology Graduate University along with the National Ryukyu Hospital, Okinawa and Kyoto University.
Okinawa Institute of Science and Technology Graduate University – OIST
Teruya, T., et al. (2021) Whole blood metabolomics of dementia patients shows classes of disease-related metabolites. PNAS. doi.org/10.1073/pnas.2022857118.