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

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

EMBO molecular medicine (2021-10-12)
Md Rezaul Islam, Lalit Kaurani, Tea Berulava, Urs Heilbronner, Monika Budde, Tonatiuh Pena Centeno, Vakthang Elerdashvili, Maria-Patapia Zafieriou, Eva Benito, Sinem M Sertel, Maria Goldberg, Fanny Senner, Janos L Kalman, Susanne Burkhardt, Anne Sophie Oepen, Mohammad Sadman Sakib, Cemil Kerimoglu, Oliver Wirths, Heike Bickeböller, Claudia Bartels, Frederic Brosseron, Katharina Buerger, Nicoleta-Carmen Cosma, Klaus Fliessbach, Michael T Heneka, Daniel Janowitz, Ingo Kilimann, Luca Kleinedam, Christoph Laske, Coraline D Metzger, Matthias H Munk, Robert Perneczky, Oliver Peters, Josef Priller, Boris S Rauchmann, Nina Roy, Anja Schneider, Annika Spottke, Eike J Spruth, Stefan Teipel, Maike Tscheuschler, Michael Wagner, Jens Wiltfang, Emrah Düzel, Frank Jessen, Silvio O Rizzoli, Wolfram-Hubertus Zimmermann, Thomas G Schulze, Peter Falkai, Farahnaz Sananbenesi, Andre Fischer
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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IMG Mouse Microglial Cell Line, IMG microglial cells recapitulate key features of microglial cell activation and may be used to study neuroinflammatory responses underlying Alzheimer′s disease.