2018 ANNUAL REPORT © 2018 CIBERNED Coordination and management of content: Miguel Medina Padilla José de Arriba-Enríquez Aina Frontera Sánchez Almudena Flores Junquera Soledad Valero Rodríguez Design and editorial coordination: OnAccent.com CIBERNED 2018 ANNUAL REPORT INDEX 005 | Letter from the Scientific Director 006 | Introduction 009 | Aims 010 | Directory of research groups and associated institutions 012 | Geographic distribution of CIBERNED research groups 013 | Organizational structure 014 | Organization chart 015 | External scientific advisory committee 016 | Consortium members 017 | Research programmes 019 | Program 1: Alzheimer’s disease and other degenerative dementias 107 | Program 2: Parkinson’s and Huntington’s disease and other degenerative movement disorders 219 | Program 3: Amyotrophic Lateral Sclerosis and other neuromuscular disorders 257 | Cooperative research 279 | International relations 291 | Scientific productivity and other activities 307 | Finantial report 333 | Index of investigators 3 4 CIBERNED 2018 ANNUAL REPORT Jesús Ávila de Grado SCIENTIFIC DIRECTOR LETTER FROM THE SCIENTIFIC DIRECTOR As in previous years, I would like to begin by highlighting the excellent work of the re- search groups that make up CIBERNED and that has allowed us, once again, to be at the forefront of the Centers in biomedical research regarding the quality of publications in high- impact index scientific journals. In order to carry out this work, we have counted on the help and collaboration of the Management Office and the Steering Committee of the Center, as well as its support staff, and the help of the Carlos III Institute of Health and the Associated Institutions. A very important novelty has been the incorporation of six new research groups to CIBERNED, led by Drs. Boada, Mir, Acevedo, Paradas, Ostas and Martínez, to whom I want to welcome to our Center, hoping and wishing, as the groups that preceded them, to carry out a rigorous, efficient and quality work. During this year, 24 scientific papers have been published with an impact index greater than 20 in journals such as the New England Journal of Medicine, Nature, Science, Nature Medicine or Lancet Neurology, and 59 papers with an index greater than 10. In addition, 10 patents remain active, two clinical guidelines have been published and 85 clinical trials are in progress. In addition, courses and seminars have been organized, and the Training Plan has continued as planned. Due to the quality of the scientific activity carried out, some of our researchers have received awards and mentions at international and national level, so on behalf of the Center, I would like to congratulate them. Finally, I would like to highlight the success of our last Congress in Santiago de Composte- la, carried out with the invaluable help of Dr. Labandeira and the collaboration of the CIEN and Queen Sofia Foundations. We continue to progress properly. Thank you all. 5 INTRODUCTION Biomedical Research Network Centers are created to promote research excellence in Bio- medicine and Health Sciences, which is carried out in the National Health System and the Science and Technology System. Behind this initiative is the purpose of generating large Translational Research Centers, of multidisciplinary and multi-institutional nature where basic, clinical and epidemiological research can be integrated, in order to develop a sin- gle common research program, focused on certain pathologies that are relevant for the National Health System due to its prevalence or that are considered strategic because of its social impact. The genesis of CIBERNED was conducted through a coordination research strategy of ex- ploiting synergies between the different groups involved in biomedical research in these areas. It seeks to promote quality research in neurodegenerative diseases being carried out within the National Health System and the Science and Technology System through the development and promotion of a Network Research structures. The goal is to promote and finance, through the Carlos III Institute of Health, Centers for Biomedical Research in the Network (CIBER) through the association of research groups, linked to the National Health System, that contribute to scientifically substantiate the programs and policies of the National Health System in the priority areas of the National R+D+I Plan. CIBERNED was In particular, the Network Center for Biomedical Re- born with the search in Neurodegenerative Diseases (CIBERNED) was born in 2006 as the heir of the Center for Re- aim of combating search in Neurological Diseases (CIEN), which to- neurodegenerative gether with the CNIO, CNIC or CNMVIS constituted the four Centers created with the mission of fight- diseases ing the most prevalent health problems of Span- ish society: cancer, cardiovascular diseases, infectious diseases and neurodegenerative disorders. As for the other Centers, a supporting foundation named CIEN Foundation was created in 2003 as the CIEN’s management body, although unlike the other Centers, it was created as the first Network Center in Spain, eventually being renamed as CIBERNED. Since 2007 the CIEN Foundation has its headquarters in the Alzheimer Center of the Reina Sofia Foundation, created with the collaboration of CIBERNED and the CIEN Foundation, and located in Vallecas (Madrid). CIBERNED was founded under the auspices of the Carlos III Institute of Health, under a co- operation agreement signed by the Government and other participating institutions with 6 CIBERNED 2018 ANNUAL REPORT the idea of creating a Research Center in which basic, clinical and population-based stud- ies are integrated in order to develop a single joint research program, focusing on certain pathologies of great importance for the National Health System either for its prevalence or because of its social impact. It has a multidisciplinary and multi-institutional character and it is aimed at boosting the impact of cutting research in neurodegenerative disorders through a Network Research Structure, thus contributing to scientifically substantiate the programs and policies of the National Health System in the priority areas of the Na- tional R+D+I Plan. CIBERNED is a research organism, endowed with legal status under the Article 6.5 of Law 30/1992 of November 26 on the Legal Regime of Public Administrations and Common Administrative Procedure. It is formed by the association of research groups, with no physical contiguity, belonging to different administrations, institutions and regional gov- ernments, from public and private sectors with research lines and goals focused on the specific common area of neurodegenerative diseases and being coordinated to achieve scientific objectives that could hardly be considered in a more restricted execution con- text. CIBERNED is governed in the internal operating rules, by way of a Regulation. Currently, the CIBERNED-CIEN Foundation CIBERNED is partnership is the only research center in made up of research Spain (and one of the few in the world) in- groups with lines and tegrated into the international network of Centres of Excellence in Neurodegeneration objectives focused on (COEN), an initiative arising from the Euro- neurodegeneration pean Union Joint Programme for Research in Neurodegenerative Diseases (JPND). This joint program constitutes an innovative collaborative research initiative created to ad- dress the growing challenges posed by this group of diseases. Its goal is to boost the impact of research by aligning existing national research programs and identifying the common objectives whose scope would benefit through joint action. Its own statutes govern CIBERNED and since the end of 2018 its activity is structured around two Scientific Programs: • Program 1: Alzheimer’s disease and other degenerative dementias. • Program 2: Parkinson’s and Huntington’s disease and other degenerative movement disorders • Program 3: Amyotrophic Lateral Sclerosis and other neuromuscular disor- ders. During 2017 CIBERNED has consisted of 50 research groups supported by different universities, hospitals and the Research Council (CSIC), each led by a principal inves- tigator or responsible. CIBERNED is a network research center, composed of research groups belonging to different Administrations and affiliated Institutions: researcher members physically work in their parent institutions they belong to while simultane- ously and actively participating on CIBERNED’s own cooperative research agenda. It should be noted that during 2018 the Carlos III Institute of Health convened, within its annual call for aid of the Strategic Action of Health (AES), the incorporation of new groups to the CIBERNED consortium. This call has allowed the incorporation of 6 new groups (a new group for Program 1, another for Program 2 and four new groups for Program 3). 7 Thus, it is the result of a collaborative partnership between different institutions and the sum of 50 research groups. Depending on the results of the scientific evaluation of the various research groups, there is the possibility to agree on the discontinuation of some groups. Depending on budget availability, it may also consider adding some new research group currently outside CIBERNED that satisfy the requirements of scientific quality and translational activity and aligns with CIBERNED priorities. The Scientific Director Office has been set since October 2011 at the Center for Molecular Biology “Severo Ochoa” (CSIC) in Madrid. The headquarters, including the General Manag- er Office