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      Neuroinflammation in Alzheimer's Disease

      research-article
      , MD 1 , 2 , , PhD 3 , , MD 4 , , PhD 5 , , PhD 2 , , PhD 6 , , MD 7 , 8 , , PhD 9 , 10 , , PhD 11 , , MD 12 , , PhD 13 , , PhD 14 , , MD 15 , , PhD 16 , , MD 17 , 18 , , MD 19 , , MD 20 , , MD 2 , 21 , 22 , , MD 23 , , MD 1 , 2 , , PhD 24 , , PhD 25 , , PhD 26 , , PhD 27 , , PhD 28 , 29 , , MD 30 , , MD 31 , , PhD 32 , , PhD 33 , , MD 34 , , PhD 35 , , PhD 36 , , MD 37 , , MD 38 , , PhD 14 , , MD 39 , , PhD 1
      The Lancet. Neurology

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          Abstract

          Increasing evidence suggests that Alzheimer's disease pathogenesis is not restricted to the neuronal compartment but strongly interacts with immunological mechanisms in the brain. Misfolded and aggregated proteins bind to pattern recognition receptors on micro- and astroglia and trigger an innate immune response, characterized by the release of inflammatory mediators, which contribute to disease progression and severity. Genome wide analysis suggests that several genes, which increase the risk for sporadic Alzheimer's disease en-code for factors that regulate glial clearance of misfolded proteins and the inflammatory reaction. External factors, including systemic inflammation and obesity are likely to interfere with the immunological processes of the brain and further promote disease progression. This re-view provides an overview on the current knowledge and focuses on the most recent and exciting findings. Modulation of risk factors and intervention with the described immune mechanisms are likely to lead to future preventive or therapeutic strategies for Alzheimer's disease.

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          Author and article information

          Journal
          101139309
          30413
          Lancet Neurol
          Lancet Neurol
          The Lancet. Neurology
          1474-4422
          1474-4465
          10 April 2018
          April 2015
          20 April 2018
          : 14
          : 4
          : 388-405
          Affiliations
          [1 ]Department of Neurology, University Hospital Bonn, Sigmund-Freud-Strasse 25, 53127 Bonn, Germany
          [2 ]German Center for Neurodegnerative Diseases (DZNE), Ludwig-Erhard-Allee 2, 53175 Bonn, Germany
          [3 ]Division of Biomedical Sciences, Center for Glial-Neuronal Interactions, University of California, Riverside, CA, USA
          [4 ]Division of Infectious Diseases, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts, USA
          [5 ]Alzheimer Research Laboratory, Department of Neurosciences, Case Western Reserve University School of Medicine, Cleveland, OH, USA
          [6 ]Department of Anesthesiology, University of Illinois, Chicago IL, USA
          [7 ]Department of Geriatrics, Johanniter Hospital, Bonn, Germany
          [8 ]European Institute for Molecular Imaging (EIMI) at the Westfalian Wilhelms University (WWU), Münster, Germany
          [9 ]Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA, USA
          [10 ]Center for Tissue Regeneration, Repair, and Restoration, VA Palo Alto Health Care System, Palo Alto/CA, USA
          [11 ]Instituto de Biomedicina de Sevilla (IBIS), Hospital Universitario Virgen del Rocio, Consejo Superior de Investigaciones Cientificas Universidad de Sevilla, Sevilla, Spain
          [12 ]Department of Neuroscience, Neuroinflammation Research Center, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, USA
          [13 ]Division of Life Science, Hong Kong University of Science and Technology, Hong Kong
          [14 ]Department of Neurology, David Geffen School of Medicine at the University of California, Los Angeles, the Geriatric, Research, and Clinical Center, Greater Los Angeles Veterans Affairs Healthcare System, Los Angeles, California, USA
          [15 ]Institute of Molecular Medicine, University of Southern Denmark, Odense, Denmark
          [16 ]Department of Biochemistry, University of Cambridge, United Kingdom
          [17 ]Faculty of Life Sciences, The University of Manchester, Manchester, United Kingdom
          [18 ]Achucarro Center for Neuroscience, IKERBASQUE, Basque Foundation for Science, 48011 Bilbao, Spain & Department of Neurosciences, University of the Basque Country UPV/EHU and CIBERNED, Leioa, Spain
          [19 ]Research Institute of Enviromental Medicine, Nagoya University/ RIKEN Brain Science Insitute, Japan
          [20 ]Department of Neurobiology, A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland
          [21 ]Institute of Innate Immunity, University of Bonn, Bonn, Germany
          [22 ]Department of Infectious Diseases and Immunology, University of Massachusetts Medical School, Worcester, Massachusetts, USA
          [23 ]Max-Planck Research Group Neuroimmunology, Center of Advanced European Studies and Research (caesar), Bonn, Germany
          [24 ]Zilkha Neurogenetic Institute, Keck School of Medicine of the University of Southern California, 1505 San Pablo Street, Room 337, Los Angeles, CA, USA
          [25 ]University of South Florida College of Medicine, Byrd Alzheimer's Institute, Department of Molecular Pharmacology and Physiology, Tampa, Florida, USA
          [26 ]Department of Immunology, Duke University Medical Center, DUMC-3010, Durham, NC, USA
          [27 ]School of Biological Sciences, Southampton General Hospital, Southampton, United Kingdom
          [28 ]Clinical and Experimental Science, University of Southampton, United Kingdom
          [29 ]Memory Assessment and Research Centre, Moorgreen Hospital, Southern Health Foundation Trust, Southampton, United Kingdom
          [30 ]LSU Neuroscience Center of Excellence, Louisiana State University Health Sciences Center School of Medicine in New Orleans, LA 70112
          [31 ]Division of Experimental Medicine, Imperial College London, Hammersmith Hospital, London, UK
          [32 ]CNRS, UMR 7225, Experimental Therapeutics of Neurodegeneration, Paris, France
          [33 ]Department of Oncology Pathology, Cancer Centrum Karolinska, Karolinska Institutet, Stockholm 17176, Sweden
          [34 ]Department of Cellular Microbiology, Max Planck Institute for Infection Biology, Berlin, Germany
          [35 ]Institute of Physiology II, Eberhard Karls University of Tübingen, Keplerstr. 15, 72074 Tübingen, Germany
          [36 ]Department of Neuroscience, University of Groningen, University Medical Centre Groningen,, A. Deusinglaan 1, 9713 AV Groningen, The Netherlands
          [37 ]Department of Medicine, University of Colorado Denver, Aurora, CO 80045, USA
          [38 ]Centre for Studies on Prevention of Alzheimer's Disease, Douglas Mental Health University Institute, and the McGill University Faculty of Medicine, Montreal, Quebec, Canada
          [39 ]Division of Infectious Disease and Immunology, Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, USA
          Author notes
          Correspondence to: Michael Heneka M.D., Prof. of Clinical Neuroscience, Dept. of Neurology, University of Bonn and German Center for Neurodegenerative Disease (DZNE), Sigmund-Freud Str. 25, 53127 Bonn, Germany, (e) michael.heneka@ 123456ukb.uni-bonn.de , (p)+49 228 28713091
          Article
          PMC5909703 PMC5909703 5909703 nihpa672931
          10.1016/S1474-4422(15)70016-5
          5909703
          25792098
          9afe4050-f2e6-41bf-97d7-a99b8f7cb80c
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