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Je něco špatně v tomto záznamu ?
Association of Rare APOE Missense Variants V236E and R251G With Risk of Alzheimer Disease
Y. Le Guen, ME. Belloy, B. Grenier-Boley, I. de Rojas, A. Castillo-Morales, I. Jansen, A. Nicolas, C. Bellenguez, C. Dalmasso, F. Küçükali, SJ. Eger, KL. Rasmussen, JQ. Thomassen, JF. Deleuze, Z. He, V. Napolioni, P. Amouyel, F. Jessen, PG....
Jazyk angličtina Země Spojené státy americké
Typ dokumentu časopisecké články, práce podpořená grantem, Research Support, N.I.H., Extramural
- MeSH
- alely MeSH
- Alzheimerova nemoc * epidemiologie genetika MeSH
- apolipoprotein E2 genetika MeSH
- apolipoprotein E4 genetika MeSH
- apolipoproteiny E genetika MeSH
- genotyp MeSH
- lidé MeSH
- věk při počátku nemoci MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, N.I.H., Extramural MeSH
Importance: The APOE ε2 and APOE ε4 alleles are the strongest protective and risk-increasing, respectively, genetic variants for late-onset Alzheimer disease (AD). However, the mechanisms linking APOE to AD-particularly the apoE protein's role in AD pathogenesis and how this is affected by APOE variants-remain poorly understood. Identifying missense variants in addition to APOE ε2 and APOE ε4 could provide critical new insights, but given the low frequency of additional missense variants, AD genetic cohorts have previously been too small to interrogate this question robustly. Objective: To determine whether rare missense variants on APOE are associated with AD risk. Design, Setting, and Participants: Association with case-control status was tested in a sequenced discovery sample (stage 1) and followed up in several microarray imputed cohorts as well as the UK Biobank whole-exome sequencing resource using a proxy-AD phenotype (stages 2 and 3). This study combined case-control, family-based, population-based, and longitudinal AD-related cohorts that recruited referred and volunteer participants. Stage 1 included 37 409 nonunique participants of European or admixed European ancestry, with 11 868 individuals with AD and 11 934 controls passing analysis inclusion criteria. In stages 2 and 3, 475 473 participants were considered across 8 cohorts, of which 84 513 individuals with AD and proxy-AD and 328 372 controls passed inclusion criteria. Selection criteria were cohort specific, and this study was performed a posteriori on individuals who were genotyped. Among the available genotypes, 76 195 were excluded. All data were retrieved between September 2015 and November 2021 and analyzed between April and November 2021. Main Outcomes and Measures: In primary analyses, the AD risk associated with each missense variant was estimated, as appropriate, with either linear mixed-model regression or logistic regression. In secondary analyses, associations were estimated with age at onset using linear mixed-model regression and risk of conversion to AD using competing-risk regression. Results: A total of 544 384 participants were analyzed in the primary case-control analysis; 312 476 (57.4%) were female, and the mean (SD; range) age was 64.9 (15.2; 40-110) years. Two missense variants were associated with a 2-fold to 3-fold decreased AD risk: APOE ε4 (R251G) (odds ratio, 0.44; 95% CI, 0.33-0.59; P = 4.7 × 10-8) and APOE ε3 (V236E) (odds ratio, 0.37; 95% CI, 0.25-0.56; P = 1.9 × 10-6). Additionally, the cumulative incidence of AD in carriers of these variants was found to grow more slowly with age compared with noncarriers. Conclusions and Relevance: In this genetic association study, a novel variant associated with AD was identified: R251G always coinherited with ε4 on the APOE gene, which mitigates the ε4-associated AD risk. The protective effect of the V236E variant, which is always coinherited with ε3 on the APOE gene, was also confirmed. The location of these variants confirms that the carboxyl-terminal portion of apoE plays an important role in AD pathogenesis. The large risk reductions reported here suggest that protein chemistry and functional assays of these variants should be pursued, as they have the potential to guide drug development targeting APOE.
1st Department of Neurology Medical School Aristotle University of Thessaloniki Thessaloniki Greece
Alzheimer Research Center and Memory Clinic Andalusian Institute for Neuroscience Málaga Spain
Alzheimer's Centre Reina Sofia CIEN Foundation Madrid Spain
Centro de Biología Molecular Severo Ochoa Universidad Autónoma de Madrid Madrid Spain
CHU de Bordeaux Pole santé publique Bordeaux France
Clinic of Neurology UH Alexandrovska Medical University Sofia Sofia Bulgaria
Complex Genetics of Alzheimer's Disease Group VIB Center for Molecular Neurology VIB Antwerp Belgium
Department of Biomedical Sciences University of Antwerp Antwerp Belgium
Department of Biomedical Sciences University of Cagliari Cagliari Italy
Department of Biomedical Surgical and Dental Sciences University of Milan Milan Italy
Department of Clinical Biochemistry Rigshospitalet Copenhagen University Hospital Copenhagen Denmark
Department of Clinical Genetics VU University Medical Centre Amsterdam the Netherlands
Department of Clinical Medicine University of Copenhagen Copenhagen Denmark
Department of Clinical Sciences and Community Health University of Milan Milan Italy
Department of Epidemiology ErasmusMC Rotterdam the Netherlands
Department of Geriatric Psychiatry University Hospital of Psychiatry Zürich Zurich Switzerland
Department of Neurology and Neurological Sciences Stanford University Palo Alto California
Department of Neurology Bordeaux University Hospital Bordeaux France
Department of Neurology ErasmusMC Rotterdam the Netherlands
Department of Neurology Hospital Universitario Donostia San Sebastian Spain
Department of Neuroscience Rita Levi Montalcini University of Torino Torino Italy
Department of Neuroscience Università Cattolica del Sacro Cuore Rome Italy
Department of Psychiatry and Behavioral Sciences Baylor College of Medicine Houston Texas
Department of Psychiatry and Psychotherapy University Medical Center Goettingen Goettingen Germany
Department of Public Health and Caring Sciences Geriatrics Uppsala University Uppsala Sweden
Department of Radiology and Nuclear Medicine ErasmusMC Rotterdam the Netherlands
Faculty of Medicine University of Lisbon Lisbon Portugal
Fondazione IRCCS Istituto Neurologico Carlo Besta Milan Italy
Fundació Docència i Recerca MútuaTerrassa Terrassa Spain
German Center for Neurodegenerative Diseases Berlin Germany
German Center for Neurodegenerative Diseases Bonn Germany
German Center for Neurodegenerative Diseases Goettingen Germany
German Center for Neurodegenerative Diseases Magdeburg Germany
German Center for Neurodegenerative Diseases Munich Germany
Institut de Recerca Biomedica de Lleida Lleida Spain
Institut du Cerveau Paris Brain Institute Paris France
Institute for Regenerative Medicine University of Zürich Zurich Switzerland
Institute for Urban Public Health University Hospital of University Duisburg Essen Essen Germany
Institute of Biomedicine University of Eastern Finland Joensuu Kuopio Finland
Institute of Clinical Medicine Neurology University of Eastern Finland Kuopio Finland
Institute of Clinical Medicine University of Oslo Oslo Norway
Institute of Neurology Catholic University of the Sacred Heart Rome Italy
Instituto de Investigacion Sanitaria 'Hospital la Paz' Madrid Spain
Instituto de Investigación Sanitaria del Principado de Asturias Oviedo Spain
International Clinical Research Center St Anne's University Hospital Brno Brno Czech Republic
IRCCS Fondazione Don Carlo Gnocchi Florence Italy
Krembil Brain Institute University Health Network Toronto Ontario Canada
Laboratorio de Genética Hospital Universitario Central de Asturias Oviedo Spain
Laboratory of Neurogenetics Born Bunge Institute Antwerp Belgium
Laboratory of Neuropsychiatry IRCCS Santa Lucia Foundation Rome Italy
Medical University of Vienna Department of Psychiatry and Psychotherapy Vienna Austria
Memory Disorders Unit Department of Neurology Hospital Universitari Mutua de Terrassa Terrassa Spain
Munich Cluster for Systems Neurology Munich Germany
Networking Research Center on Neurodegenerative Diseases Instituto de Salud Carlos 3 Madrid Spain
Neurodegenerative Diseases Unit Fondazione IRCCS Ca' Granda Ospedale Policlinico Milan Italy
Neurological Tissue Bank Hospital Clinic IDIBAPS Barcelona Spain
Neurology San Gerardo Hospital Monza and University of Milano Bicocca Milan Italy
Neurology Service Marqués de Valdecilla University Hospital Santander Spain
Neurology Unit IRCCS Fondazione Policlinico Universitario A Gemelli Rome Italy
Neuroscience Center Zurich University of Zurich and ETH Zurich Zurich Switzerland
Neurosciences Area Instituto Biodonostia San Sebastian Spain
NORMENT Centre Division of Mental Health and Addiction Oslo University Hospital Oslo Norway
Nuffield Department of Population Health Oxford University Oxford United Kingdom
Old Age Psychiatry Department of Psychiatry Lausanne University Hospital Lausanne Switzerland
Quantitative Sciences Unit Department of Medicine Stanford University Palo Alto California
School of Biosciences and Veterinary Medicine University of Camerino Camerino Italy
School of Medicine Cardiff University Cardiff United Kingdom
Translational Health Sciences Bristol Medical School University of Bristol Bristol United Kingdom
Unidad Mixta de Neurologia Genètica Instituto de Investigación Sanitaria La Fe Valencia Spain
Unit for Hereditary Dementias Theme Aging Karolinska University Hospital Solna Stockholm Sweden
Unit of Neurology University of Parma Parma Italy
Unitat de Genètica Molecular Institut de Biomedicina de València CSIC Valencia Spain
Unitat Trastorns Cognitius Hospital Universitari Santa Maria de Lleida Lleida Spain
Université de Paris EA 4468 APHP Hôpital Broca Paris France
Université Paris Saclay CEA Centre National de Recherche en Génomique Humaine Evry France
University Bordeaux Inserm Bordeaux Population Health Research Center Bordeaux France
Zurich Center for Integrative Human Physiology University of Zurich Zurich Switzerland
Citace poskytuje Crossref.org
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- $a Le Guen, Yann $u Department of Neurology and Neurological Sciences, Stanford University, Palo Alto, California $u Institut du Cerveau, Paris Brain Institute, Paris, France
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- $a Association of Rare APOE Missense Variants V236E and R251G With Risk of Alzheimer Disease / $c Y. Le Guen, ME. Belloy, B. Grenier-Boley, I. de Rojas, A. Castillo-Morales, I. Jansen, A. Nicolas, C. Bellenguez, C. Dalmasso, F. Küçükali, SJ. Eger, KL. Rasmussen, JQ. Thomassen, JF. Deleuze, Z. He, V. Napolioni, P. Amouyel, F. Jessen, PG. Kehoe, C. van Duijn, M. Tsolaki, P. Sánchez-Juan, K. Sleegers, M. Ingelsson, G. Rossi, M. Hiltunen, R. Sims, WM. van der Flier, A. Ramirez, OA. Andreassen, R. Frikke-Schmidt, J. Williams, A. Ruiz, JC. Lambert, MD. Greicius, Members of the EADB, GR@ACE, DEGESCO, DemGene, GERAD, and EADI Groups, B. Arosio, L. Benussi, A. Boland, B. Borroni, P. Caffarra, D. Daian, A. Daniele, S. Debette, C. Dufouil, E. Düzel, D. Galimberti, V. Giedraitis, T. Grimmer, C. Graff, E. Grünblatt, O. Hanon, L. Hausner, S. Heilmann-Heimbach, H. Holstege, J. Hort, D. Jürgen, T. Kuulasmaa, A. van der Lugt, C. Masullo, P. Mecocci, S. Mehrabian, A. de Mendonça, S. Moebus, B. Nacmias, G. Nicolas, R. Olaso, G. Papenberg, L. Parnetti, F. Pasquier, O. Peters, YAL. Pijnenburg, J. Popp, I. Rainero, I. Ramakers, S. Riedel-Heller, N. Scarmeas, P. Scheltens, N. Scherbaum, A. Schneider, D. Seripa, H. Soininen, V. Solfrizzi, G. Spalletta, A. Squassina, J. van Swieten, TJ. Tegos, L. Tremolizzo, F. Verhey, M. Vyhnalek, J. Wiltfang, M. Boada, P. García-González, R. Puerta, LM. Real, V. Álvarez, MJ. Bullido, J. Clarimon, JM. García-Alberca, P. Mir, F. Moreno, P. Pastor, G. Piñol-Ripoll, L. Molina-Porcel, J. Pérez-Tur, E. Rodríguez-Rodríguez, JL. Royo, R. Sánchez-Valle, M. Dichgans, D. Rujescu
- 520 9_
- $a Importance: The APOE ε2 and APOE ε4 alleles are the strongest protective and risk-increasing, respectively, genetic variants for late-onset Alzheimer disease (AD). However, the mechanisms linking APOE to AD-particularly the apoE protein's role in AD pathogenesis and how this is affected by APOE variants-remain poorly understood. Identifying missense variants in addition to APOE ε2 and APOE ε4 could provide critical new insights, but given the low frequency of additional missense variants, AD genetic cohorts have previously been too small to interrogate this question robustly. Objective: To determine whether rare missense variants on APOE are associated with AD risk. Design, Setting, and Participants: Association with case-control status was tested in a sequenced discovery sample (stage 1) and followed up in several microarray imputed cohorts as well as the UK Biobank whole-exome sequencing resource using a proxy-AD phenotype (stages 2 and 3). This study combined case-control, family-based, population-based, and longitudinal AD-related cohorts that recruited referred and volunteer participants. Stage 1 included 37 409 nonunique participants of European or admixed European ancestry, with 11 868 individuals with AD and 11 934 controls passing analysis inclusion criteria. In stages 2 and 3, 475 473 participants were considered across 8 cohorts, of which 84 513 individuals with AD and proxy-AD and 328 372 controls passed inclusion criteria. Selection criteria were cohort specific, and this study was performed a posteriori on individuals who were genotyped. Among the available genotypes, 76 195 were excluded. All data were retrieved between September 2015 and November 2021 and analyzed between April and November 2021. Main Outcomes and Measures: In primary analyses, the AD risk associated with each missense variant was estimated, as appropriate, with either linear mixed-model regression or logistic regression. In secondary analyses, associations were estimated with age at onset using linear mixed-model regression and risk of conversion to AD using competing-risk regression. Results: A total of 544 384 participants were analyzed in the primary case-control analysis; 312 476 (57.4%) were female, and the mean (SD; range) age was 64.9 (15.2; 40-110) years. Two missense variants were associated with a 2-fold to 3-fold decreased AD risk: APOE ε4 (R251G) (odds ratio, 0.44; 95% CI, 0.33-0.59; P = 4.7 × 10-8) and APOE ε3 (V236E) (odds ratio, 0.37; 95% CI, 0.25-0.56; P = 1.9 × 10-6). Additionally, the cumulative incidence of AD in carriers of these variants was found to grow more slowly with age compared with noncarriers. Conclusions and Relevance: In this genetic association study, a novel variant associated with AD was identified: R251G always coinherited with ε4 on the APOE gene, which mitigates the ε4-associated AD risk. The protective effect of the V236E variant, which is always coinherited with ε3 on the APOE gene, was also confirmed. The location of these variants confirms that the carboxyl-terminal portion of apoE plays an important role in AD pathogenesis. The large risk reductions reported here suggest that protein chemistry and functional assays of these variants should be pursued, as they have the potential to guide drug development targeting APOE.
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- 700 1_
- $a Dalmasso, Carolina $u Department of Psychiatry and Psychotherapy, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany $u Estudios en Neurociencias y Sistemas Complejos (ENyS) CONICET-HEC-UNAJ, Universidad Nacional Arturo Jauretche, Florencio Varela, Argentina
- 700 1_
- $a Küçükali, Fahri $u Complex Genetics of Alzheimer's Disease Group, VIB Center for Molecular Neurology, VIB, Antwerp, Belgium $u Laboratory of Neurogenetics, Born-Bunge Institute, Antwerp, Belgium $u Department of Biomedical Sciences, University of Antwerp, Antwerp, Belgium
- 700 1_
- $a Eger, Sarah J $u Department of Neurology and Neurological Sciences, Stanford University, Palo Alto, California
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- 700 1_
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- 700 1_
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- 700 1_
- $a He, Zihuai $u Department of Neurology and Neurological Sciences, Stanford University, Palo Alto, California $u Quantitative Sciences Unit, Department of Medicine, Stanford University, Palo Alto, California
- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
- $a Jürgen, Deckert $u Department of Psychiatry, Psychosomatics and Psychotherapy, Center of Mental Health, University Hospital of Würzburg, Würzburg, Germany
- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
- $a Nicolas, Gael $u Normandie Université, UNIROUEN, Inserm U1245 and CHU Rouen, Department of Genetics and CNR-MAJ, Rouen, France
- 700 1_
- $a Olaso, Robert $u Université Paris-Saclay, CEA, Centre National de Recherche en Génomique Humaine, Evry, France
- 700 1_
- $a Papenberg, Goran $u Aging Research Center, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet and Stockholm University, Stockholm, Sweden
- 700 1_
- $a Parnetti, Lucilla $u Centre for Memory Disturbances, Lab of Clinical Neurochemistry, Section of Neurology, University of Perugia, Perugia, Italy
- 700 1_
- $a Pasquier, Florence $u Université de Lille, Inserm 1172, CHU Clinical and Research Memory Research Centre (CMRR) of Distalz, Lille, France
- 700 1_
- $a Peters, Oliver $u German Center for Neurodegenerative Diseases (DZNE), Berlin, Germany $u Charité - Universitätsmedizin Berlin, Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Institute of Psychiatry and Psychotherapy, Berlin, Germany
- 700 1_
- $a Pijnenburg, Yolande A L $u Alzheimer Center Amsterdam, Department of Neurology, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam UMC, Amsterdam, the Netherlands
- 700 1_
- $a Popp, Julius $u Old Age Psychiatry, Department of Psychiatry, Lausanne University Hospital, Lausanne, Switzerland $u Department of Geriatric Psychiatry, University Hospital of Psychiatry Zürich, Zurich, Switzerland $u Institute for Regenerative Medicine, University of Zürich, Zurich, Switzerland
- 700 1_
- $a Rainero, Innocenzo $u Department of Neuroscience "Rita Levi Montalcini," University of Torino, Torino, Italy
- 700 1_
- $a Ramakers, Inez $u Maastricht University, Department of Psychiatry and Neuropsychologie, Alzheimer Center Limburg, Maastricht, the Netherlands
- 700 1_
- $a Riedel-Heller, Steffi $u Institute of Social Medicine, Occupational Health and Public Health, University of Leipzig, Leipzig, Germany
- 700 1_
- $a Scarmeas, Nikolaos $u 1st Department of Neurology, Aiginition Hospital, National and Kapodistrian University of Athens, Medical School, Athens, Greece $u Taub Institute for Research in Alzheimer's Disease and the Aging Brain, The Gertrude H. Sergievsky Center, Department of Neurology, Columbia University, New York, New York
- 700 1_
- $a Scheltens, Philip $u Alzheimer Center Amsterdam, Department of Neurology, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam UMC, Amsterdam, the Netherlands
- 700 1_
- $a Scherbaum, Norbert $u LVR-Hospital Essen, Department of Psychiatry and Psychotherapy, Medical Faculty, University of Duisburg-Essen, Essen, Germany
- 700 1_
- $a Schneider, Anja $u German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany $u Department of Neurodegenerative Diseases and Geriatric Psychiatry, University Hospital Bonn, Bonn, Germany
- 700 1_
- $a Seripa, Davide $u Laboratory for Advanced Hematological Diagnostics, Department of Hematology and Stem Cell Transplant, "Vito Fazzi" Hospital, Lecce, Italy
- 700 1_
- $a Soininen, Hilkka $u Institute of Clinical Medicine - Neurology, University of Eastern Finland, Kuopio, Finland
- 700 1_
- $a Solfrizzi, Vincenzo $u Interdisciplinary Department of Medicine, Geriatric Medicine and Memory Unit, University of Bari Aldo Moro, Bari, Italy
- 700 1_
- $a Spalletta, Gianfranco $u Laboratory of Neuropsychiatry, IRCCS Santa Lucia Foundation, Rome, Italy $u Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine, Houston, Texas
- 700 1_
- $a Squassina, Alessio $u Department of Biomedical Sciences, University of Cagliari, Cagliari, Italy
- 700 1_
- $a van Swieten, John $u Department of Neurology, ErasmusMC, Rotterdam, the Netherlands
- 700 1_
- $a Tegos, Thomas J $u 1st Department of Neurology, Medical School, Aristotle University of Thessaloniki, Thessaloniki, Greece
- 700 1_
- $a Tremolizzo, Lucio $u Neurology, "San Gerardo" Hospital, Monza and University of Milano-Bicocca, Milan, Italy
- 700 1_
- $a Verhey, Frans $u Maastricht University, Department of Psychiatry and Neuropsychologie, Alzheimer Center Limburg, Maastricht, the Netherlands
- 700 1_
- $a Vyhnalek, Martin $u Memory Clinic, Department of Neurology, Charles University, 2nd Faculty of Medicine and Motol University Hospital, Prague, Czech Republic $u International Clinical Research Center, St Anne's University Hospital Brno, Brno, Czech Republic
- 700 1_
- $a Wiltfang, Jens $u Department of Psychiatry and Psychotherapy, University Medical Center Goettingen, Goettingen, Germany $u German Center for Neurodegenerative Diseases (DZNE), Goettingen, Germany $u Neurosciences and Signaling Group, Institute of Biomedicine (iBiMED), Department of Medical Sciences, University of Aveiro, Aveiro, Portugal
- 700 1_
- $a Boada, Mercè $u Research Center and Memory Clinic Fundació ACE, Institut Català de Neurociències Aplicades, Universitat Internacional de Catalunya, Barcelona, Spain $u Networking Research Center on Neurodegenerative Diseases (CIBERNED), Instituto de Salud Carlos III, Madrid, Spain
- 700 1_
- $a García-González, Pablo $u Research Center and Memory Clinic Fundació ACE, Institut Català de Neurociències Aplicades, Universitat Internacional de Catalunya, Barcelona, Spain $u Networking Research Center on Neurodegenerative Diseases (CIBERNED), Instituto de Salud Carlos III, Madrid, Spain
- 700 1_
- $a Puerta, Raquel $u Research Center and Memory Clinic Fundació ACE, Institut Català de Neurociències Aplicades, Universitat Internacional de Catalunya, Barcelona, Spain
- 700 1_
- $a Real, Luis M $u Unidad Clínica de Enfermedades Infecciosas y Microbiología, Hospital Universitario de Valme, Sevilla, Spain $u Depatamento de Especialidades Quirúrgicas, Bioquímica e Inmunología, Facultad de Medicina, Universidad de Málaga, Málaga, Spain
- 700 1_
- $a Álvarez, Victoria $u Laboratorio de Genética, Hospital Universitario Central de Asturias, Oviedo, Spain $u Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Oviedo, Spain
- 700 1_
- $a Bullido, María J $u Networking Research Center on Neurodegenerative Diseases (CIBERNED), Instituto de Salud Carlos III, Madrid, Spain $u Centro de Biología Molecular Severo Ochoa (UAM-CSIC), Universidad Autónoma de Madrid, Madrid, Spain $u Instituto de Investigacion Sanitaria 'Hospital la Paz' (IdIPaz), Madrid, Spain
- 700 1_
- $a Clarimon, Jordi $u Networking Research Center on Neurodegenerative Diseases (CIBERNED), Instituto de Salud Carlos III, Madrid, Spain $u Department of Neurology, II B Sant Pau, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain
- 700 1_
- $a García-Alberca, José María $u Networking Research Center on Neurodegenerative Diseases (CIBERNED), Instituto de Salud Carlos III, Madrid, Spain $u Alzheimer Research Center & Memory Clinic, Andalusian Institute for Neuroscience, Málaga, Spain
- 700 1_
- $a Mir, Pablo $u Networking Research Center on Neurodegenerative Diseases (CIBERNED), Instituto de Salud Carlos III, Madrid, Spain $u Unidad de Trastornos del Movimiento, Servicio de Neurología y Neurofisiología, Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Seville, Spain
- 700 1_
- $a Moreno, Fermin $u Networking Research Center on Neurodegenerative Diseases (CIBERNED), Instituto de Salud Carlos III, Madrid, Spain $u Department of Neurology, Hospital Universitario Donostia, San Sebastian, Spain $u Neurosciences Area, Instituto Biodonostia, San Sebastian, Spain
- 700 1_
- $a Pastor, Pau $u Fundació Docència i Recerca MútuaTerrassa, Terrassa, Spain $u Memory Disorders Unit, Department of Neurology, Hospital Universitari Mutua de Terrassa, Terrassa, Spain
- 700 1_
- $a Piñol-Ripoll, Gerard $u Unitat Trastorns Cognitius, Hospital Universitari Santa Maria de Lleida, Lleida, Spain $u Institut de Recerca Biomedica de Lleida (IRBLLeida), Lleida, Spain
- 700 1_
- $a Molina-Porcel, Laura $u Neurological Tissue Bank (Biobanc), Hospital Clinic IDIBAPS, Barcelona, Spain $u Alzheimer's Disease and Other Cognitive Disorders Unit, Neurology Department, Hospital Clinic, Barcelona, Spain
- 700 1_
- $a Pérez-Tur, Jordi $u Networking Research Center on Neurodegenerative Diseases (CIBERNED), Instituto de Salud Carlos III, Madrid, Spain $u Unitat de Genètica Molecular, Institut de Biomedicina de València-CSIC, Valencia, Spain $u Unidad Mixta de Neurologia Genètica, Instituto de Investigación Sanitaria La Fe, Valencia, Spain
- 700 1_
- $a Rodríguez-Rodríguez, Eloy $u Networking Research Center on Neurodegenerative Diseases (CIBERNED), Instituto de Salud Carlos III, Madrid, Spain $u Neurology Service, Marqués de Valdecilla University Hospital (University of Cantabria and IDIVAL), Santander, Spain
- 700 1_
- $a Royo, Jose Luís $u Depatamento de Especialidades Quirúrgicas, Bioquímica e Inmunología, Facultad de Medicina, Universidad de Málaga, Málaga, Spain
- 700 1_
- $a Sánchez-Valle, Raquel $u Alzheimer's Disease and Other Cognitive Disorders Unit, Service of Neurology, Hospital Clínic of Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer, University of Barcelona, Barcelona, Spain
- 700 1_
- $a Dichgans, Martin $u Institute for Stroke and Dementia Research (ISD), University Hospital, Ludwig Maximilian University of Munich, Munich, Germany $u German Center for Neurodegenerative Diseases (DZNE), Munich, Germany $u Munich Cluster for Systems Neurology (SyNergy), Munich, Germany
- 700 1_
- $a Rujescu, Dan $u Medical University of Vienna, Department of Psychiatry and Psychotherapy, Vienna, Austria
- 710 2_
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