Levels of Certain microRNAs Indicate Risk for Cognitive Decline
From:
The DZNE (Deutsches Zentrum für Neurodegenerative Erkrankungen) and the
University Medical Center Gottingen (UMG)
October 11, 2021 -- Researchers at the
DZNE and the University Medical Center Göttingen (UMG) have identified
molecules in the blood that can 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 levels
of so-called microRNAs.
The technique is not yet suitable for
practical use; the scientists therefore aim to develop a simple blood test that
can be applied in routine medical care to assess dementia risk. According to
the study data, microRNAs could potentially also be targets for dementia therapy.
“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,”
says André Fischer, research group leader and spokesperson at the DZNE site in
Göttingen and professor at the Department of Psychiatry and Psychotherapy at
UMG. “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.”
Molecular Signature
The biomarker that Fischer and his
colleagues have found is based on measuring so-called microRNAs in the blood.
MicroRNAs are molecules with regulatory properties: they influence the
production of proteins and thus a key process in the metabolism of every living
being. “There are many different microRNAs and each of them can regulate entire
networks of interdependent proteins and thus influence complex processes in the
organism. 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,” Fischer says.
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). For the data from healthy individuals,
the Göttingen scientists cooperated with Munich University Hospital. The data
from MCI patients came from a DZNE study that has been running for years and
involves university clinics throughout Germany.
Omens of Dementia
In the end, the various findings came
together like pieces of a puzzle: 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.”
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 establish connections with each other. 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.”
Application in Routine Care
The novel marker still requires further
testing; moreover, the current measurement procedure is too complex for
practical use: “In further studies, we aim to validate this biomarker
clinically. In addition, we intend to develop a simple test procedure for
point-of-care screening,” says Fischer. “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. 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.”
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