“Harbinger” molecules could predict dementia up to 5 years in advance
Earlier detection of dementia could open up far more effective ways to treat and manage the condition, and one place scientists are increasingly turning to for warning signs is the blood. A new study has further broadened the possibilities in this area, pinpointing a set of molecules the authors describe as a "harbinger" of the condition two to five years ahead of onset, and may even provide new targets for advanced therapies.
In the past few years, we have seen a flurry of research pointing to the possibility of a blood test for dementia, with a particular focus on Alzheimer's disease. Many of these breakthroughs are based on the detection of precursors for the toxic brain plaques associated with the condition, while some have also focused on genetic material and lipid biomarkers.
The new study, carried out by scientists at the German Center for Neurodegenerative Diseases (DZNE) and the University Medical Center Göttingen, takes aim at molecules call microRNA. These are short strands of non-coding RNA that can regulate gene expression and protein production, and we've seen recently how they could play a role in cancer diagnosis through blood and even urine tests.
“There are many different microRNAs and each of them can regulate entire networks of interdependent proteins and thus influence complex processes in the organism," says Professor André Fischer, who led the research team. "So, microRNAs have a broad impact. We wanted to find out whether there are specific microRNAs whose presence in the blood correlates with mental fitness."
In order to pinpoint a set of microRNAs that can act as a signature for mental performance, the scientists analyzed data on young, healthy subjects and elderly people with mild cognitive impairment (MCI). These efforts were helped along by extensive studies in mice and cell cultures, with the team landing on three microRNAs that acted as a marker for mental performance.
In the young and healthy subjects, the lower levels of these microRNAs in the blood correlated with better performance in cognitive tests. In the mice, the levels began to escalate even before they began to exhibit a deterioration in mental performance, while in the patients with MCI, 90 percent of those with high levels of the blood marker went on to develop Alzheimer's disease within two years.
“We therefore see an increased blood level of these three microRNAs as a harbinger of dementia,” Fischer says. “We estimate that in humans this biomarker indicates a development that is about two to five years in the future.”
Further to connecting these three microRNAs to dementia, the scientists also uncovered some insights into how they might actually drive the condition. Through their research on mice and cell cultures, it was found that the trio of molecules shape inflammatory process in the brain and affect neuroplasticity, or the ability of neurons to form connections.
“In our view, they are not only markers, but also have an active impact on pathological processes. This makes them potential targets for therapy,” Fischer says. “Indeed, we see in mice that learning ability improves when these microRNAs are blocked with drugs. We’ve observed this in mice with age-related mental deficits, as well as in mice with brain damage similar to that occurring in Alzheimer’s disease.”
While results of the study are indeed promising for advancing early detection of dementia, the scientists are under no illusions about the challenges involved in turning it into a blood test for clinical use. As it stands, the microRNAs can only be measured through a complex procedure that is not viable for such applications, but by further validating the biomarkers and then developing a point-of-care screening solution, the scientists are working toward such a future.
“Our goal is to have a low-cost test, similar to the rapid test for SARS-CoV-2 with the difference that for our purposes, you would need a drop of blood," says Fisher. "Such a test could be used during routine checkups in doctors’ practices to detect an elevated risk of dementia early on. Individuals with suspicious results could then undergo more elaborate diagnostics.”
The research was published in the journal EMBO Molecular Medicine.