[en] Increasing evidence suggests that Alzheimer's disease pathogenesis is not restricted to the neuronal compartment, but includes strong interactions with immunological mechanisms in the brain. Misfolded and aggregated proteins bind to pattern recognition receptors on microglia and astroglia, and trigger an innate immune response characterised by release of inflammatory mediators, which contribute to disease progression and severity. Genome-wide analysis suggests that several genes that increase the risk for sporadic Alzheimer's disease encode factors that regulate glial clearance of misfolded proteins and the inflammatory reaction. External factors, including systemic inflammation and obesity, are likely to interfere with immunological processes of the brain and further promote disease progression. Modulation of risk factors and targeting of these immune mechanisms could lead to future therapeutic or preventive strategies for Alzheimer's disease.
Disciplines :
Neurology
Author, co-author :
HENEKA, Michael ; Department of Neurology, University Hospital Bonn, University of Bonn, Bonn, Germany, German Center for Neurodegnerative Diseases (DZNE), Bonn, Germany. Electronic address: michael.heneka@ukb.uni-bonn.de
Carson, Monica J; Division of Biomedical Sciences, Center for Glial-Neuronal Interactions, University of California, Riverside, CA, USA
El Khoury, Joseph; Division of Infectious Diseases, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA
Landreth, Gary E; Alzheimer Research Laboratory, Department of Neurosciences, Case Western Reserve University School of Medicine, Cleveland, OH, USA
Brosseron, Frederic; German Center for Neurodegnerative Diseases (DZNE), Bonn, Germany
Feinstein, Douglas L; Department of Anesthesiology, University of Illinois, Chicago, IL, USA
Jacobs, Andreas H; Department of Geriatrics, Johanniter Hospital, Bonn, Germany, European Institute for Molecular Imaging (EIMI) at the Westfalian Wilhelms University (WWU), Münster, Germany
Wyss-Coray, Tony; Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA, USA, Center for Tissue Regeneration, Repair, and Restoration, VA Palo Alto Health Care System, Palo Alto, CA, USA
Vitorica, Javier; Instituto de Biomedicina de Sevilla (IBIS), Hospital Universitario Virgen del Rocio, Consejo Superior de Investigaciones Cientificas Universidad de Sevilla, Sevilla, Spain
Ransohoff, Richard M; Department of Neuroscience, Neuroinflammation Research Center, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA
Herrup, Karl; Division of Life Science, Hong Kong University of Science and Technology, Hong Kong
Frautschy, Sally A; 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, CA, USA
Finsen, Bente; Institute of Molecular Medicine, University of Southern Denmark, Odense, Denmark
Brown, Guy C; Department of Biochemistry, University of Cambridge, Cambridge, UK
Verkhratsky, Alexei; Faculty of Life Sciences, The University of Manchester, Manchester, UK, Achucarro Center for Neuroscience, Basque Foundation for Science (IKERBASQUE), Bilbao, Spain, Department of Neurosciences, University of the Basque Country UPV/EHU (Euskal Herriko Unibertsitatea/Universidad del País Vasco) and CIBERNED (Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas), Leioa, Spain
Yamanaka, Koji; Research Institute of Environmental Medicine, Nagoya University/RIKEN Brain Science Institute, Wako-shi, Japan
Koistinaho, Jari; Department of Neurobiology, AI Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland
Latz, Eicke; German Center for Neurodegnerative Diseases (DZNE), Bonn, Germany, Institute of Innate Immunity, University of Bonn, Bonn, Germany, Department of InfectiousDiseases and Immunology, University of Massachusetts Medical School, Worcester, MA, USA
Halle, Annett; Max-Planck Research Group Neuroimmunology, Center of Advanced European Studies and Research (CAESAR), Bonn, Germany
Petzold, Gabor C; Department of Neurology, University Hospital Bonn, University of Bonn, Bonn, Germany, German Center for Neurodegnerative Diseases (DZNE), Bonn, Germany
Town, Terrence; Zilkha Neurogenetic Institute, Keck School of Medicine of the University of Southern California, Los Angeles, CA, USA
Morgan, Dave; Department of Molecular Pharmacology and Physiology, Byrd Alzheimer's Institute, University of South Florida College of Medicine, Tampa, FL, USA
Shinohara, Mari L; Department of Immunology, Duke University Medical Center, Durham, NC, USA
Perry, V Hugh; School of Biological Sciences, Southampton General Hospital, Southampton, UK
Holmes, Clive; Clinical and Experimental Science, University of Southampton, Southampton, UK, Memory Assessment and Research Centre, Moorgreen Hospital, Southern Health Foundation Trust, Southampton, UK
Bazan, Nicolas G; Louisiana State University Neuroscience Center of Excellence, Louisiana State University Health Sciences Center School of Medicine in New Orleans, LA, USA
Brooks, David J; Division of Experimental Medicine, Imperial College London, Hammersmith Hospital, London, UK
Hunot, Stéphane; Centre National de la Recherche Scientifique (CNRS), UMR 7225, Experimental Therapeutics of Neurodegeneration, Paris, France
Joseph, Bertrand; Department of Oncology Pathology, Cancer Centrum Karolinska, Karolinska Institutet, Stockholm, Sweden
Deigendesch, Nikolaus; Department of Cellular Microbiology, Max Planck Institute for Infection Biology, Berlin, Germany
Garaschuk, Olga; Institute of Physiology II, Eberhard Karls University of Tübingen, Tübingen, Germany
Boddeke, Erik; Department of Neuroscience, University of Groningen, University Medical Centre Groningen, Groningen, Netherlands
Dinarello, Charles A; Department of Medicine, University of Colorado Denver, Aurora, CO, USA
Breitner, John C; Centre for Studies on Prevention of Alzheimer's Disease, Douglas Mental Health University Institute, and the McGill University Faculty of Medicine, Montreal, Quebec, Canada
Cole, Greg M; 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, CA, USA
Golenbock, Douglas T; Department of InfectiousDiseases and Immunology, University of Massachusetts Medical School, Worcester, MA, USA
Kummer, Markus P; Department of Neurology, University Hospital Bonn, University of Bonn, Bonn, Germany
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