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A microRNA signature that correlates with cognition and is a target against cognitive decline

Islam, Md Rezaul, Kaurani, Lalit, Berulava, Tea, Heilbronner, Urs, Budde, Monika, Centeno, Tonatiuh Pena, Elerdashvili, Vakthang, Zafieriou, Maria‐Patapia, Benito, Eva, Sertel, Sinem M, Goldberg, Maria, Senner, Fanny, Kalman, Janos L, Burkhardt, Susanne, Oepen, Anne Sophie, Sakib, Mohammad Sadman, Kerimoglu, Cemil, Wirths, Oliver, Bickeböller, Heike, Bartels, Claudia, Brosseron, Frederic, Buerger, Katharina, Cosma, Nicoleta‐Carmen, Fliessbach, Klaus, Heneka, Michael T., Janowitz, Daniel, Kilimann, Ingo, Kleinedam, Luca, Laske, Christoph, Metzger, Coraline D, Munk, Matthias H, Perneczky, Robert, Peters, Oliver, Priller, Josef, Rauchmann, Boris S., Roy, Nina, Schneider, Anja, Spottke, Annika, Spruth, Eike J, Teipel, Stefan, Tscheuschler, Maike, Wagner, Michael, Wiltfang, Jens, Düzel, Emrah, Jessen, Frank, Delcode Study Group, Rizzoli, Silvio O, Zimmermann, Wolfram‐Hubertus, Schulze, Thomas G, Falkai, Peter, Sananbenesi, Farahnaz, Fischer, Andre·2021·EMBO Molecular Medicine
DOI 10.15252/emmm.202013659PMC PMC8573587
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Abstract

While some individuals age without pathological memory impairments, others develop age‐associated cognitive diseases. Since changes in cognitive function develop slowly over time in these patients, they are often diagnosed at an advanced stage of molecular pathology, a time point when causative treatments fail. Thus, there is great need for the identification of inexpensive and minimal invasive approaches that could be used for screening with the aim to identify individuals at risk for cognitive decline that can then undergo further diagnostics and eventually stratified therapies. In this study, we use an integrative approach combining the analysis of human data and mechanistic studies in model systems to identify a circulating 3‐microRNA signature that reflects key processes linked to neural homeostasis and inform about cognitive status. We furthermore provide evidence that expression changes in this signature represent multiple mechanisms deregulated in the aging and diseased brain and are a suitable target for RNA therapeutics.

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Metadata

Authors
Islam, M. R., Kaurani, L., Berulava, T., Heilbronner, U., Budde, M., Centeno, T. P., Elerdashvili, V., Zafieriou, M., Benito, E., Sertel, S. M., Goldberg, M., Senner, F., Kalman, J. L., Burkhardt, S., Oepen, A. S., Sakib, M. S., Kerimoglu, C., Wirths, O., Bickeböller, H., Bartels, C., Brosseron, F., Buerger, K., Cosma, N., Fliessbach, K., Heneka, M. T., Janowitz, D., Kilimann, I., Kleinedam, L., Laske, C., Metzger, C. D., Munk, M. H., Perneczky, R., Peters, O., Priller, J., Rauchmann, B. S., Roy, N., Schneider, A., Spottke, A., Spruth, E. J., Teipel, S., Tscheuschler, M., Wagner, M., Wiltfang, J., Düzel, E., Jessen, F., Delcode Study Group, Rizzoli, S. O., Zimmermann, W., Schulze, T. G., Falkai, P., Sananbenesi, F., & Fischer, A.
ORCID
Venue
EMBO Molecular Medicine
Publisher
Springer Science and Business Media LLC
Published
2021-10-11
Volume
13
Issue
11
ISSN
  • 1757-4676
  • 1757-4684
DOI
10.15252/emmm.202013659
PMC
PMC8573587
Cited by
74
References
26
Language
en
Licence
Funders
  • H2020 European Research Council (DEPICODE 648898)
  • Deutsche Forschungsgemeinschaft (SPP1738, SCHU1603/4‐1 5‐1 71, KFO241/PsyCourse FA241/16‐1, SA1005/2, EXC 2067/1 390729940, SFB1286, KFO241/PsyCourse,FI981‐4,11‐1, FI981‐4,15‐1)
  • Bundesministerium für Bildung und Forschung (Integrament,01ZX1314D, 01EE1404H, 01ZX1614K, ENERGI,01GQ1421A)
  • Common Fund (GMP LiPSC‐GR1.1)

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