Differential expression of microRNAs in Alzheimer's disease brain,blood, and cerebrospinal fluid |
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| Affiliation: | 1. Ageing Epidemiology (AGE) Research Unit, School of Public Health, Imperial College London, London, UK;2. Genetic and Molecular Epidemiology Group, Lübeck Interdisciplinary Platform for Genome Analytics (LIGA), Institutes of Neurogenetics & Cardiogenetics, University of Lübeck, Lübeck, Germany;3. Lübeck Interdisciplinary Platform for Genome Analytics (LIGA), Institutes of Neurogenetics & Cardiogenetics, University of Lübeck, Lübeck, Germany;4. Department of Psychiatry and Psychotherapy, University Hospital, LMU Munich, Munich, Germany;5. German Center for Neurodegenerative Diseases (DZNE) Munich, Munich, Germany;6. Munich Cluster for Systems Neurology (SyNergy), Munich, Germany;7. Department of Psychology, University of Oslo, Oslo, Norway;1. Department of Psychiatry, University of Oxford, Oxford, UK;2. Lübeck Interdisciplinary Platform for Genome Analytics, Institutes of Neurogenetics and Cardiogenetics, University of Lübeck, Lübeck, Germany;3. Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, Kiel, Germany;4. Maurice Wohl Clinical Neuroscience, Institute of Psychiatry, Psychology and Neuroscience, Kings College London, London, UK;5. Department of Psychiatry and Neurochemistry, University of Gothenburg, Mölndal, Sweden;6. Wallenberg Centre for Molecular & Translational Medicine, University of Gothenburg, Gothenburg, Sweden;7. NIHR Biomedical Research Centre for Mental Health and Biomedical Research Unit for Dementia at South London and Maudsley NHS Foundation, London, UK;8. Dementia Research Institute Cardiff, Cardiff University, Cardiff, UK;9. Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Alzheimer Centrum Limburg, Maastricht University, Maastricht, the Netherlands;10. Alzheimer Center, VU University Medical Center, Amsterdam, the Netherlands;11. University Hospital Leuven, Leuven, Belgium;12. Laboratory for Cognitive Neurology, Department of Neurosciences, KU Leuven, Belgium;13. Center for Neurosciences, Vrije Universiteit Brussel (VUB), Brussels, Belgium;14. Reference Center for Biological Markers of Dementia (BIODEM), University of Antwerp, Antwerp, Belgium;15. Institute Born-Bunge, University of Antwerp, Antwerp, Belgium;p. Department of Neurology, VUB University Hospital Brussels (UZ Brussel), Brussels, Belgium;q. Neurodegenerative Brain Diseases Group, Center for Molecular Neurology, VIB, Edegem, Belgium;r. University of Geneva, Geneva, Switzerland;s. IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, Brescia, Italy;t. AIX Marseille University, INS, Ap-hm, Marseille, France;u. Neurosciences Therapeutic Area, GlaxoSmithKline R&D, Stevenage, UK;v. University of Lille, Inserm, CHU Lille, Lille, France;w. Alzheimer''s disease & other cognitive disorders unit, Hopsital Clínic-IDIBAPS, Barcelona, Spain;x. Barcelona Beta Brain Research Center, Universitat Pompeu Fabra, Barcelona, Spain;y. Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden;z. Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK;11. 1st Department of Neurology, AHEPA University Hospital, Makedonia, Thessaloniki, Greece;22. Hospital de la Santa Creu i Sant Pau, Barcelona, Spain;33. Department of Neurology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain;44. University Hospital of Lausanne, Lausanne, Switzerland;55. Geriatric Psychiatry, Department of Mental Health and Psychiatry, Geneva University Hospitals, Geneva, Switzerland;66. CITA-Alzheimer Foundation, San Sebastian, Spain;77. Danish Dementia Research Centre, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark;88. Neurochemistry Laboratory, Department of Clinical Chemistry, Amsterdam Neuroscience, Amsterdam University Medical Centers, Vrije Universiteit, Amsterdam, The Netherlands;99. Department of Neurobiology, Caring Sciences and Society (NVS), Division of Clinical Geriatrics, Karolinska Institutet, and Department of Geriatric Medicine, Karolinska University Hospital Huddinge, Stockholm, Sweden;1010. Department of Psychiatry in Region Örebro County and School of Medical Sciences, Faculty of Medicine and Health, Örebro University, Örebro, Sweden;1111. Department of Old Age Psychiatry, Psychology and Neuroscience, Kings College London, London, UK;1212. Department of Geriatric Psychiatry, Zentralinstitut für Seelische Gesundheit, University of Heidelberg, Mannheim, Germany;1313. Kings College London, London, UK;1414. The Systems Medicine Group, Steno Diabetes Center, Gentofte, Denmark;1515. Department of Radiology and Nuclear Medicine, VU University Medical Center, Amsterdam, The Netherland;pp. UCL Institutes of Neurology and Healthcare Engineering, London, UK;qq. Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden;rr. UK Dementia Research Institute at UCL, London, UK;ss. Department of Neurodegenerative Disease, UCL Institute of Neurology, London, UK;tt. Janssen R&D, Titusville, NJ, USA;uu. Janssen R&D, LLC, Beerse, Belgium;vv. Department of Neurobiology, Care Sciences and Society, Division of Neurogeriatrics, Karolinska Institutet, Stockholm, Sweden;ww. Department of Psychology, University of Oslo, Oslo, Norway;xx. Janssen-Cilag UK, formerly Department of Psychiatry, University of Oxford, Oxford, UK;1. Clinical Bioinformatics, Saarland University, Saarbrücken, Germany;2. Internal Medicine, Heidelberg University, Heidelberg, Germany;3. Department for Human Genetics, Saarland University Hospital, Homburg, Germany;4. Department of Neurodegeneration and Hertie-Institute of Clinical Brain Research of the Eberhard-Karls-University, German Center for Neurodegenerative Diseases, Tübingen, Germany;5. Department of Neurology, Charité - Universitätsmedizin Berlin, Berlin, Germany;6. Siemens Healthcare, Erlangen, Germany;7. Krankenhaus Lindenbrunn, Lindenbrunn, Germany;1. Department of Neurology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, PR China;2. Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan, PR China;3. Center for Medical Genetics, Central South University, Changsha, Hunan, PR China;4. National Clinical Research Center for Geriatric Diseases, Changsha, Hunan, PR China;5. Key Laboratory of Hunan Province in Neurodegenerative Disorders, Central South University, Changsha, Hunan, PR China;1. Division of Biostatistics, Washington University School of Medicine, St. Louis, MO, USA;2. Knight Alzheimer''s Disease Research Center, Washington University School of Medicine, St. Louis, MO, USA;3. Division of Public Health Sciences, Department of Surgery, Washington University School of Medicine, St. Louis, MO, USA;4. Siteman Cancer Center Biostatistics Core Washington University School of Medicine, St. Louis, MO, USA;5. Department of Neurology, Washington University School of Medicine, St. Louis, MO, USA;6. Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA;7. Wisconsin Alzheimer''s Institute and Alzheimer''s Disease Research Center, University of Wisconsin-Madison School of Medicine and Public Health, Madison, WI, USA;8. Geriatric Research Education and Clinical Center, William S Middleton Veterans Memorial Hospital, Madison, WI, USA;9. The Florey Institute, University of Melbourne, Melbourne, Australia;10. Department of Molecular Imaging & Therapy, Austin Health, Heidelberg, Australia;11. Department of Medicine, University of Melbourne, Melbourne, Australia;12. Department of Radiology, Washington University School of Medicine, St. Louis, MO, USA;13. Departments of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA;1. Department of Pediatric Surgery, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China;2. Department of Neurology, Ann Romney Center for Neurologic Diseases, Brigham and Women''s Hospital, Harvard Medical School, Boston, MA, USA;1. Doctoral Programme in Experimental Biology and Biomedicine, CNC - Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal;2. Institute for Interdisciplinary Research, University of Coimbra, Coimbra, Portugal;3. CNC - Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal;4. Faculty of Medicine, University of Coimbra, Coimbra, Portugal;5. Memory Clinic, Neurology Department, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal;6. Department of Life Sciences, Faculty of Science and Technology, University of Coimbra, Coimbra, Portugal |
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| Abstract: | IntroductionSeveral microRNAs (miRNAs) have been implicated in Alzheimer's disease pathogenesis, but the evidence from individual case-control studies remains inconclusive.MethodsA systematic literature review was performed, followed by standardized multistage data extraction, quality control, and meta-analyses on eligible data for brain, blood, and cerebrospinal fluid specimens. Results were compared with miRNAs reported in the abstracts of eligible studies or recent qualitative reviews to assess novelty.ResultsData from 147 independent data sets across 107 publications were quantitatively assessed in 461 meta-analyses. Twenty-five, five, and 32 miRNAs showed studywide significant differential expression (α < 1·08 × 10−4) in brain, cerebrospinal fluid, and blood-derived specimens, respectively, with 5 miRNAs showing differential expression in both brain and blood. Of these 57 miRNAs, 13 had not been reported in the abstracts of previous original or review articles.DiscussionOur systematic assessment of differential miRNA expression is the first of its kind in Alzheimer's disease and highlights several miRNAs of potential relevance. |
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| Keywords: | Alzheimer's disease Dementia Genetics Epigenetics Biomarker Meta-analysis Systematic review Diagnosis Prognosis Pathophysiology |
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