[en] Over the past few decades, research on Alzheimer's disease (AD) has focused on pathomechanisms linked to two of the major pathological hallmarks of extracellular deposition of beta-amyloid peptides and intra-neuronal formation of neurofibrils. Recently, a third disease component, the neuroinflammatory reaction mediated by cerebral innate immune cells, has entered the spotlight, prompted by findings from genetic, pre-clinical, and clinical studies. Various proteins that arise during neurodegeneration, including beta-amyloid, tau, heat shock proteins, and chromogranin, among others, act as danger-associated molecular patterns, that-upon engagement of pattern recognition receptors-induce inflammatory signaling pathways and ultimately lead to the production and release of immune mediators. These may have beneficial effects but ultimately compromise neuronal function and cause cell death. The current review, assembled by participants of the Chiclana Summer School on Neuroinflammation 2016, provides an overview of our current understanding of AD-related immune processes. We describe the principal cellular and molecular players in inflammation as they pertain to AD, examine modifying factors, and discuss potential future therapeutic targets.
Disciplines :
Neurology
Author, co-author :
Ardura-Fabregat, A; Faculty of Medicine, Institute of Neuropathology, University of Freiburg, Freiburg, Germany
Boddeke, E W G M; Department of Neuroscience, Section Medical Physiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
Boza-Serrano, A; Experimental Neuroinflammation Laboratory, Department of Experimental Medical Sciences, Biomedical Centrum (BMC), Lund University, Lund, Sweden
Brioschi, S; Department of Psychiatry and Psychotherapy, Medical Center University of Freiburg, Faculty of Medicine University of Freiburg, Freiburg, Germany
Castro-Gomez, S; Department of Neurodegenerative Disease and Gerontopsychiatry/Neurology, University of Bonn Medical Center, Sigmund-Freud Str. 25, 53127, Bonn, Germany
Ceyzériat, K; Commissariat à l'Energie Atomique et aux Energies Alternatives (CEA), Département de la Recherche Fondamentale (DRF), Institut de biologie François Jacob, MIRCen, 92260, Fontenay-aux-Roses, France ; Neurodegenerative Diseases Laboratory, Centre National de la Recherche Scientifique (CNRS), Université Paris-Sud, UMR 9199, F-92260, Fontenay-aux-Roses, France
Dansokho, C; German Center for Neurodegenerative Diseases (DZNE), Sigmund Freud Str. 27, 53127, Bonn, Germany
Dierkes, T; German Center for Neurodegenerative Diseases (DZNE), Sigmund Freud Str. 27, 53127, Bonn, Germany ; Biomedical Centre, Institute of Innate Immunity, University Hospital Bonn, Sigmund-Freud-Str. 25, 53127, Bonn, Germany
Gelders, G; Department of Neurosciences, Laboratory for Neurobiology and Gene Therapy, KU Leuven, Leuven, Belgium
HENEKA, Michael ; German Center for Neurodegenerative Diseases (DZNE), Sigmund Freud Str. 27, 53127, Bonn, Germany. michael.heneka@ukbonn.de ; Department of Neurodegenerative Disease and Gerontopsychiatry/Neurology, University of Bonn Medical Center, Sigmund-Freud Str. 25, 53127, Bonn, Germany. michael.heneka@ukbonn.de
Hoeijmakers, L; Center for Neuroscience (SILS-CNS), Swammerdam Institute for Life Sciences, University of Amsterdam, Amsterdam, The Netherlands
Hoffmann, A; Department of Molecular Neurology, University Hospital Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany
Iaccarino, L; Vita-Salute San Raffaele University, Milan, Italy ; In Vivo Human Molecular and Structural Neuroimaging Unit, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy
Jahnert, S; Department of Neurodegenerative Disease and Gerontopsychiatry/Neurology, University of Bonn Medical Center, Sigmund-Freud Str. 25, 53127, Bonn, Germany
Kuhbandner, K; Department of Neurology, University Hospital Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany
Landreth, G; Stark Neuroscience Research Institute, Indiana University School of Medicine, Indianapolis, IN, 46202, USA
Lonnemann, N; Department of Cellular Neurobiology, Zoological Institute, Technische Universität Braunschweig, Braunschweig, Germany
Löschmann, P A; Pfizer Deutschland GmbH, Berlin, Germany
McManus, R M; German Center for Neurodegenerative Diseases (DZNE), Sigmund Freud Str. 27, 53127, Bonn, Germany
Paulus, A; Experimental Neuroinflammation Laboratory, Department of Experimental Medical Sciences, Biomedical Centrum (BMC), Lund University, Lund, Sweden
Reemst, K; Center for Neuroscience (SILS-CNS), Swammerdam Institute for Life Sciences, University of Amsterdam, Amsterdam, The Netherlands
Sanchez-Caro, J M; German Center for Neurodegenerative Diseases (DZNE), Sigmund Freud Str. 27, 53127, Bonn, Germany
Tiberi, A; Bio@SNS Laboratory, Scuola Normale Superiore, Piazza dei Cavalieri 7, 56126, Pisa, Italy
Van der Perren, A; Department of Neurosciences, Laboratory for Neurobiology and Gene Therapy, KU Leuven, Leuven, Belgium
Vautheny, A; Commissariat à l'Energie Atomique et aux Energies Alternatives (CEA), Département de la Recherche Fondamentale (DRF), Institut de biologie François Jacob, MIRCen, 92260, Fontenay-aux-Roses, France ; Neurodegenerative Diseases Laboratory, Centre National de la Recherche Scientifique (CNRS), Université Paris-Sud, UMR 9199, F-92260, Fontenay-aux-Roses, France
Venegas, C; Department of Neurodegenerative Disease and Gerontopsychiatry/Neurology, University of Bonn Medical Center, Sigmund-Freud Str. 25, 53127, Bonn, Germany
Webers, A; Department of Neurodegenerative Disease and Gerontopsychiatry/Neurology, University of Bonn Medical Center, Sigmund-Freud Str. 25, 53127, Bonn, Germany
Weydt, P; Department of Neurodegenerative Disease and Gerontopsychiatry/Neurology, University of Bonn Medical Center, Sigmund-Freud Str. 25, 53127, Bonn, Germany
Wijasa, T S; German Center for Neurodegenerative Diseases (DZNE), Sigmund Freud Str. 27, 53127, Bonn, Germany
Xiang, X; Biomedical Center (BMC), Biochemistry, Ludwig-Maximilians-University Munich, 81377, Munich, Germany ; Graduate School of Systemic Neuroscience, Ludwig-Maximilians-University, Munich, 82152, Munich, Germany
Yang, Y; Experimental Neuroinflammation Laboratory, Department of Experimental Medical Sciences, Biomedical Centrum (BMC), Lund University, Lund, Sweden
The authors thank Ildiko Racz and Cathy Widmann for editorial assistance. No outside funding was used for this article. The open access fee was covered by University of Bonn.
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