Researchers find warning signs for dementia in the blood
Levels of certain microRNAs indicate risk for cognitive decline

Date:
October 11, 2021
Source:
DZNE - German Center for Neurodegenerative Diseases
Summary:
Researchers have identified molecules in the blood that can indicate
impending dementia. Their findings are based on human studies and
laboratory experiments. The biomarker is based on measuring levels
of so- called microRNAs. According to the study data, microRNAs
could potentially also be targets for dementia therapy.



FULL STORY ========================================================================== Researchers at the DZNE and the University Medical Center Go"ttingen
(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. Andre' 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 Andre' Fischer, research group leader and spokesperson at the DZNE
site in Go"ttingen 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 Go"ttingen 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 elevates risk of dementia early on. Individuals
with suspicious results could then undergo more elaborate diagnostics." ========================================================================== Story Source: Materials provided by DZNE_-_German_Center_for_Neurodegenerative_Diseases.

Note: Content may be edited for style and length.


========================================================================== Journal Reference:
1. Rezaul Islam, Lalit Kaurani et al. A microRNA-signature that
correlates
with cognition and is a target against cognitive decline. EMBO
Molecular Medicine, 2021 DOI: 10.15252/emmm.202013659 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2021/10/211011091258.htm

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