title: Neuroinflammation in Alzheimer's disease.
abstract: 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.
authors: 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.
authors: Michael T
authors: MT
authors: Heneka
authors: Division of Biomedical Sciences, Center for Glial-Neuronal Interactions, University of California, Riverside, CA, USA.
authors: Monica J
authors: MJ
authors: Carson
authors: Division of Infectious Diseases, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA.
authors: Joseph
authors: J
authors: El Khoury
authors: Alzheimer Research Laboratory, Department of Neurosciences, Case Western Reserve University School of Medicine, Cleveland, OH, USA.
authors: Gary E
authors: GE
authors: Landreth
authors: German Center for Neurodegnerative Diseases (DZNE), Bonn, Germany.
authors: Frederic
authors: F
authors: Brosseron
authors: Department of Anesthesiology, University of Illinois, Chicago, IL, USA.
authors: Douglas L
authors: DL
authors: Feinstein
authors: Department of Geriatrics, Johanniter Hospital, Bonn, Germany; European Institute for Molecular Imaging (EIMI) at the Westfalian Wilhelms University (WWU), Münster, Germany.
authors: Andreas H
authors: AH
authors: Jacobs
authors: 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.
authors: Tony
authors: T
authors: Wyss-Coray
authors: Instituto de Biomedicina de Sevilla (IBIS), Hospital Universitario Virgen del Rocio, Consejo Superior de Investigaciones Cientificas Universidad de Sevilla, Sevilla, Spain.
authors: Javier
authors: J
authors: Vitorica
authors: Department of Neuroscience, Neuroinflammation Research Center, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA.
authors: Richard M
authors: RM
authors: Ransohoff
authors: Division of Life Science, Hong Kong University of Science and Technology, Hong Kong.
authors: Karl
authors: K
authors: Herrup
authors: 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.
authors: Sally A
authors: SA
authors: Frautschy
authors: Institute of Molecular Medicine, University of Southern Denmark, Odense, Denmark.
authors: Bente
authors: B
authors: Finsen
authors: Department of Biochemistry, University of Cambridge, Cambridge, UK.
authors: Guy C
authors: GC
authors: Brown
authors: 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.
authors: Alexei
authors: A
authors: Verkhratsky
authors: Research Institute of Environmental Medicine, Nagoya University/RIKEN Brain Science Institute, Wako-shi, Japan.
authors: Koji
authors: K
authors: Yamanaka
authors: Department of Neurobiology, AI Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland.
authors: Jari
authors: J
authors: Koistinaho
authors: 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.
authors: Eicke
authors: E
authors: Latz
authors: Max-Planck Research Group Neuroimmunology, Center of Advanced European Studies and Research (CAESAR), Bonn, Germany.
authors: Annett
authors: A
authors: Halle
authors: Department of Neurology, University Hospital Bonn, University of Bonn, Bonn, Germany; German Center for Neurodegnerative Diseases (DZNE), Bonn, Germany.
authors: Gabor C
authors: GC
authors: Petzold
authors: Zilkha Neurogenetic Institute, Keck School of Medicine of the University of Southern California, Los Angeles, CA, USA.
authors: Terrence
authors: T
authors: Town
authors: Department of Molecular Pharmacology and Physiology, Byrd Alzheimer's Institute, University of South Florida College of Medicine, Tampa, FL, USA.
authors: Dave
authors: D
authors: Morgan
authors: Department of Immunology, Duke University Medical Center, Durham, NC, USA.
authors: Mari L
authors: ML
authors: Shinohara
authors: School of Biological Sciences, Southampton General Hospital, Southampton, UK.
authors: V Hugh
authors: VH
authors: Perry
authors: Clinical and Experimental Science, University of Southampton, Southampton, UK; Memory Assessment and Research Centre, Moorgreen Hospital, Southern Health Foundation Trust, Southampton, UK.
authors: Clive
authors: C
authors: Holmes
authors: Louisiana State University Neuroscience Center of Excellence, Louisiana State University Health Sciences Center School of Medicine in New Orleans, LA, USA.
authors: Nicolas G
authors: NG
authors: Bazan
authors: Division of Experimental Medicine, Imperial College London, Hammersmith Hospital, London, UK.
authors: David J
authors: DJ
authors: Brooks
authors: Centre National de la Recherche Scientifique (CNRS), UMR 7225, Experimental Therapeutics of Neurodegeneration, Paris, France.
authors: Stéphane
authors: S
authors: Hunot
authors: Department of Oncology Pathology, Cancer Centrum Karolinska, Karolinska Institutet, Stockholm, Sweden.
authors: Bertrand
authors: B
authors: Joseph
authors: Department of Cellular Microbiology, Max Planck Institute for Infection Biology, Berlin, Germany.
authors: Nikolaus
authors: N
authors: Deigendesch
authors: Institute of Physiology II, Eberhard Karls University of Tübingen, Tübingen, Germany.
authors: Olga
authors: O
authors: Garaschuk
authors: Department of Neuroscience, University of Groningen, University Medical Centre Groningen, Groningen, Netherlands.
authors: Erik
authors: E
authors: Boddeke
authors: Department of Medicine, University of Colorado Denver, Aurora, CO, USA.
authors: Charles A
authors: CA
authors: Dinarello
authors: Centre for Studies on Prevention of Alzheimer's Disease, Douglas Mental Health University Institute, and the McGill University Faculty of Medicine, Montreal, Quebec, Canada.
authors: John C
authors: JC
authors: Breitner
authors: 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.
authors: Greg M
authors: GM
authors: Cole
authors: Department of InfectiousDiseases and Immunology, University of Massachusetts Medical School, Worcester, MA, USA.
authors: Douglas T
authors: DT
authors: Golenbock
authors: Department of Neurology, University Hospital Bonn, University of Bonn, Bonn, Germany.
authors: Markus P
authors: MP
authors: Kummer
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D001253:Astrocytes / Q000276:immunology / Q000473:pathology; D015415:Biomarkers / Q000097:blood / Q000134:cerebrospinal fluid; D001930:Brain Injuries / Q000150:complications* / Q000378:metabolism; D002986:Clinical Trials as Topic; D004195:Disease Models, Animal; D018450:Disease Progression; D006801:Humans; D007113:Immunity, Innate; D007114:Immunization; D007249:Inflammation / Q000175:diagnosis / Q000276:immunology / Q000378:metabolism*; D018836:Inflammation Mediators / Q000276:immunology / Q000378:metabolism*; D008125:Locus Coeruleus / Q000473:pathology; D017628:Microglia / Q000276:immunology* / Q000473:pathology*; D018697:Nootropic Agents / Q000008:administration & dosage; D009765:Obesity / Q000150:complications* / Q000378:metabolism; D010587:Phagocytosis; D017510:Protein Folding; D012307:Risk Factors; D012720:Severity of Illness Index
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D015415:Biomarkers; D018836:Inflammation Mediators; D018697:Nootropic Agents