gms | German Medical Science

Joint-Meeting of the German Society for Neuropathology and Neuroanatomy (DGNN) and the Scandinavian Neuropathological Society (SNS)

Deutsche Gesellschaft für Neuropathologie und Neuroanatomie

22.09.-24.09.2016, Hamburg

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APOE signaling is a common pathway in microglia in neurodegeneration

Meeting Abstract

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  • presenting/speaker Susanne Krasemann - University Medical Center Hamburg-Eppendorf UKE, Institute for Neuropathology, Hamburg, Germany; Harvard Medical School, Brigham and Womens Hospital, Boston, United States
  • Charlotte Madore - Harvard Medical School, Brigham and Womens Hospital, Boston, United States
  • Elaine O´Loughlin - Harvard Medical School, Brigham and Womens Hospital, Boston, United States
  • Ron Cialic - Harvard Medical School, Brigham and Womens Hospital, Boston, United States
  • Zain Fanek - Harvard Medical School, Brigham and Womens Hospital, Boston, United States
  • Rachid El Fatimy - Harvard Medical School, Brigham and Womens Hospital, Boston, United States
  • David Greco - Harvard Medical School, Brigham and Womens Hospital, Boston, United States
  • Scott Smith - Harvard Medical School, Brigham and Womens Hospital, Boston, United States
  • Georg Tweet - Harvard Medical School, Brigham and Womens Hospital, Boston, United States
  • Fargol Mazaheri - German Center for Neurodegenerative Diseases (DZNE), Munich, Germany
  • Patricia Conde-Sanroman - Icahn School of Medicine at Mount Sinai, Department of Medicine, New York, United States
  • Mar Garcias - Icahn School of Medicine at Mount Sinai, Department of Medicine, New York, United States
  • Narghes Calcagno - Harvard Medical School, Brigham and Womens Hospital, Boston, United States
  • Markus Glatzel - University Medical Center Hamburg-Eppendorf UKE, Institute for Neuropathology, Hamburg, Germany
  • Anna Worthmann - University Medical Center Hamburg-Eppendorf UKE, Department of Biochemistry and Molecular Cell Biology, Hamburg, Germany
  • Joerg Heeren - University Medical Center Hamburg-Eppendorf UKE, Department of Biochemistry and Molecular Cell Biology, Hamburg, Germany
  • Cynthia Lemere - Harvard Medical School, Brigham and Womens Hospital, Boston, United States
  • Charles Vanderburg - Harvard Medical School, Harvard NeuroDiscovery Center, Boston, United States
  • Frank Heppner - Charité – Universitätsmedizin Berlin, Institute for Neuropathology, Berlin, Germany
  • Bogdan Budnik - MSPRL, Center for Systems Biology, Boston, United States
  • Tsuneya Ikezu - Boston University School of Medicine, Boston, United States
  • Hans Lassmann - Medical University of Vienna, Center for Brain Research, Vienna, Austria
  • Howard Weiner - Harvard Medical School, Brigham and Womens Hospital, Boston, United States
  • Jordi Ochando - Icahn School of Medicine at Mount Sinai, Department of Medicine, New York, United States
  • Christian Haass - German Center for Neurodegenerative Diseases (DZNE), Munich, Germany
  • Oleg Butovsky - Harvard Medical School, Brigham and Womens Hospital, Boston, United States

Deutsche Gesellschaft für Neuropathologie und Neuroanatomie. Scandinavian Neuropathological Society. Joint-Meeting of the German Society for Neuropathology and Neuroanatomy (DGNN) and the Scandinavian Neuropathological Society (SNS). Hamburg, 22.-24.09.2016. Düsseldorf: German Medical Science GMS Publishing House; 2016. Doc16dgnnND5

doi: 10.3205/16dgnn09, urn:nbn:de:0183-16dgnn091

Veröffentlicht: 14. September 2016

© 2016 Krasemann et al.
Dieser Artikel ist ein Open-Access-Artikel und steht unter den Lizenzbedingungen der Creative Commons Attribution 4.0 License (Namensnennung). Lizenz-Angaben siehe http://creativecommons.org/licenses/by/4.0/.

Gliederung

Text

Microglia are the immune cells of the brain. They play a dual role by promoting homeostatic functions in the healthy brain, but acquiring dysregulated properties in neurodegenerative and neuroinflammatory diseases. How this switch in the microglia phenotype is executed on the molecular level is still unknown. We identified a common microglial molecular signature in neurodegenerative conditions in mouse models of Alzheimer’s disease, Multiple Sclerosis and Amyotrophic Lateral Sclerosis. This phenotype is characterized by the significant suppression of TGFβ1 and upregulation of Apoe-expression and in striking contrast to the classical M1 activation after LPS stimulation. Microglial switch from the homeostatic to the disease associated phenotype is initiated via recognition and phagocytosis of apoptotic neurons and neuronal fragments, leading to suppression of microglia homeostatic signature in an APOE-dependent manner. Genetic targeting of Apoe restores the TGFβ-dependent homeostatic signature. Taken together, we show that TGFβ-APOE pathway is a regulatory signaling in microglia in neurodegenerative diseases and supports future development of microglia-targeted therapeutics.