A microRNA signature that correlates with cognition and is a target against cognitive decline
Rezaul Islam, Lalit Kaurani, Tea Berulava, Urs Heilbronner, Monika Budde, Tonatiuh Peña Centeno, Vakthang Elerdashvili, Maria‐Patapia Zafieriou, Eva Benito, Sinem M. Sertel, Maria Goldberg, Fanny Senner, János Kálmán, Susanne Burkhardt, Anne S. Oepen, M. Sadman Sakib, Cemil Kerimoglu, Oliver Wirths, Heike Bickeböller, Claudia Bartels, Frederic Brosseron, Katharina Büerger, 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‐Stephan Rauchmann, Nina Roy, Anja Schneider, Annika Spottke, Eike Spruth, Stefan Teipel, Maike Tscheuschler, Michael Wagner, Jens Wiltfang, Emrah Düzel, Frank Jessen, Delcode Study Group, Silvio O. Rizzoli, Wolfram‐Hubertus Zimmermann, Thomas G. Schulze, Peter Falkai, Farahnaz Sananbenesi, André 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.