title: Young microglia restore amyloid plaque clearance of aged microglia.
abstract: Alzheimer's disease (AD) is characterized by deposition of amyloid plaques, neurofibrillary tangles, and neuroinflammation. In order to study microglial contribution to amyloid plaque phagocytosis, we developed a novelex vivomodel by co-culturing organotypic brain slices from up to 20-month-old, amyloid-bearing AD mouse model (APPPS1) and young, neonatal wild-type (WT) mice. Surprisingly, co-culturing resulted in proliferation, recruitment, and clustering of old microglial cells around amyloid plaques and clearance of the plaque halo. Depletion of either old or young microglial cells prevented amyloid plaque clearance, indicating a synergistic effect of both populations. Exposing old microglial cells to conditioned media of young microglia or addition of granulocyte-macrophage colony-stimulating factor (GM-CSF) was sufficient to induce microglial proliferation and reduce amyloid plaque size. Our data suggest that microglial dysfunction in AD may be reversible and their phagocytic ability can be modulated to limit amyloid accumulation. This novelex vivomodel provides a valuable system for identification, screening, and testing of compounds aimed to therapeutically reinforce microglial phagocytosis.
authors.affiliation: Biomedical Center (BMC), Ludwig-Maximilians Universität München, Munich, Germany.
authors.forename: Anna
authors.initials: A
authors.lastname: Daria
authors.affiliation: German Center for Neurodegenerative Diseases (DZNE) Munich, Munich, Germany.
authors.forename: Alessio
authors.initials: A
authors.lastname: Colombo
authors.affiliation: Institute for Stroke and dementia research (ISD), Ludwig-Maximilians Universität München, Munich, Germany.
authors.forename: Gemma
authors.initials: G
authors.lastname: Llovera
authors.affiliation: Biomedical Center (BMC), Ludwig-Maximilians Universität München, Munich, Germany.
authors.forename: Heike
authors.initials: H
authors.lastname: Hampel
authors.affiliation: Biomedical Center (BMC), Ludwig-Maximilians Universität München, Munich, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Willem
authors.affiliation: Institute for Stroke and dementia research (ISD), Ludwig-Maximilians Universität München, Munich, Germany.|Munich Cluster for Systems Neurology (SyNergy), Munich, Germany.
authors.forename: Arthur
authors.initials: A
authors.lastname: Liesz
authors.affiliation: Biomedical Center (BMC), Ludwig-Maximilians Universität München, Munich, Germany christian.haass@mail03.med.uni-muenchen.de sabina.tahirovic@dzne.de.|German Center for Neurodegenerative Diseases (DZNE) Munich, Munich, Germany.|Munich Cluster for Systems Neurology (SyNergy), Munich, Germany.
authors.forename: Christian
authors.identifier: 0000-0002-4869-1627
authors.initials: C
authors.lastname: Haass
authors.affiliation: German Center for Neurodegenerative Diseases (DZNE) Munich, Munich, Germany christian.haass@mail03.med.uni-muenchen.de sabina.tahirovic@dzne.de.
authors.forename: Sabina
authors.identifier: 0000-0003-4403-9559
authors.initials: S
authors.lastname: Tahirovic
mesh_terms: D000544:Alzheimer Disease / Q000473:pathology*; D000818:Animals; D001921:Brain / Q000473:pathology*; D049109:Cell Proliferation; D018920:Coculture Techniques; D017077:Culture Media, Conditioned; D004195:Disease Models, Animal; D051379:Mice; D017628:Microglia / Q000378:metabolism* / Q000502:physiology; D009924:Organ Culture Techniques; D058225:Plaque, Amyloid / Q000378:metabolism*
chemical_list: D017077:Culture Media, Conditioned
keywords: Alzheimer's disease; amyloid plaque clearance; microglia; neurodegeneration