Researchers find molecules in blood that may indicate impending dementia

Researchers from the DZNE and the University Medical Center Göttingen (UMG) have identified molecules in the blood that may indicate impending dementia. Their findings, which are presented in the scientific journal “EMBO Molecular Medicine“, are based on human studies and laboratory experiments. Various university hospitals across Germany were also involved in the investigations.

The biomarker described by the team led by Prof. André Fischer is based on measuring the levels of what are called microRNAs. The technique is not yet suitable for practical use; scientists therefore aim to develop a simple blood test that can be applied in routine medical care to assess the risk of dementia. According to study data, microRNAs could also be targeted for the treatment of dementia.

“When the symptoms of dementia come on, the brain has already been severely damaged. At present, the diagnosis is made far too late to even have a chance of having effective treatment. If dementia is detected early, the chances of positively influencing the course of the disease increase ”explains André Fischer, head of the research group and spokesperson for the DZNE site in Göttingen and professor at the Department of Psychiatry and Psychotherapy at the ‘UMG. “We need tests that respond ideally before the onset of dementia and reliably estimate the risk of subsequent disease. In other words, tests that give an early warning. We are confident that the results of our studies current ones pave the way for such tests. “

Molecular signature

The biomarker that Fischer and his colleagues found is based on measuring so-called microRNAs in blood. MicroRNAs are molecules with regulatory properties: they influence the production of proteins and therefore a key process in the metabolism of all living things. “There are many different microRNAs and each of them can regulate entire networks of interrelated proteins and thus influence complex processes in the organism. MicroRNAs therefore have a broad impact. We wanted to know if there are specific microRNAs that exist. presence in the blood correlates with good mental fitness, ”says Fischer.

Through extensive studies in humans, mice, and cell cultures, the researchers finally identified three microRNAs whose levels were associated with mental performance. To do this, they analyzed data from both cognitively normal young individuals and elderly people with mild cognitive impairment (MCI). For data from healthy individuals, scientists from Göttingen cooperated with the University Hospital Munich. The MCI patient data comes from a DZNE study that has been going on for years and involves university clinics across Germany.

Portents of dementia

In the end, the different findings came together like pieces of a puzzle: In healthy individuals, microRNA levels correlated with mental fitness. The lower the blood level, the better the subjects’ performance in cognition tests. In mice, in turn, this score increased even before the rodents began to show mental decline – whether due to age or because they developed symptoms similar to those of dementia. Alzheimer’s.

Further evidence came from patients with MCI: Among those in whom the blood marker was very high, about 90 percent developed Alzheimer’s disease within two years. “So we see an increase in the blood level of these three microRNAs as a warning sign of dementia,” explains Fischer. “We estimate that in humans, this biomarker indicates development in about two to five years.”

Potential targets for therapy

In their studies on mice and cell cultures, the researchers also found that the three identified microRNAs influence inflammatory processes in the brain and “neuroplasticity,” which includes the ability of neurons to make connections with each other. This suggests that the three microRNAs are more than warning signals. “In our opinion, these are not only markers, but they also have an active impact on disease processes. This makes them potential targets for therapy, ”explains Fischer. “Indeed, we see in mice that learning ability improves when these microRNAs are blocked by drugs. We have observed this in mice with age-related mental deficits, as well as in mice with brain damage similar to that seen in Alzheimer’s disease. “

Application in routine care

The new marker still requires additional testing; in addition, the current measurement procedure is too complex for practical use: “In other studies, we aim to validate this biomarker clinically. In addition, we intend to develop a simple testing procedure for point-of-care screening, ”explains Fischer. “Our goal is to have a low cost test, similar to the rapid test for SARS-CoV-2 except that for our purposes you would need a drop of blood. Such a test could be used in routine examinations by doctors’ to detect a high risk of dementia early on. People with suspicious results could then undergo more elaborate diagnoses. “