Researchers at the DZNE and the University Medical Center Göttingen (UMG) have identified three circulating microRNAs that they say can indicate impending dementia. Their findings were published today in EMBO Molecular Medicine.
“When symptoms of dementia manifest, the brain has already been massively damaged. Presently, diagnosis happens far too late to even have a chance for effective treatment. If dementia is detected early, the odds of positively influencing the course of the disease increase,” explains André Fischer, senior author of the paper. “We need tests that ideally respond before the onset of dementia and reliably estimate the risk of later disease. In other words, tests that give an early warning. We are confident that our current study results pave the way for such tests.”
Through extensive studies in humans, mice, and cell cultures, the researchers ultimately identified three microRNAs whose levels were associated with mental performance. For this, they analyzed data from both young, cognitively normal individuals and from elderly people with mild cognitive impairment (MCI).
The team found that in healthy individuals, levels of microRNAs correlated with mental fitness. The lower the blood level, the better the subjects performed in cognition tests. In mice, in turn, this score increased even before the rodents started to show mental decline, regardless of whether this was due to age or because they developed symptoms similar to those of Alzheimer’s dementia. Further evidence came from patients with MCI: Of those in whom the blood marker was highly elevated, about 90 percent developed 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.”
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. This suggests that the three microRNAs are more than warning signals. “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.”