title: Forebrain microglia from wild-type but not adult 5xFAD mice prevent amyloid-β plaque formation in organotypic hippocampal slice cultures.
abstract: The role of microglia in amyloid-β (Aβ) deposition is controversial. In the present study, an organotypic hippocampal slice culture (OHSC) system with an in vivo-like microglial-neuronal environment was used to investigate the potential contribution of microglia to Aβ plaque formation. We found that microglia ingested Aβ, thereby preventing plaque formation in OHSCs. Conversely, Aβ deposits formed rapidly in microglia-free wild-type slices. The capacity to prevent Aβ plaque formation was absent in forebrain microglia from young adult but not juvenile 5xFamilial Alzheimer's disease (FAD) mice. Since no loss of Aβ clearance capacity was observed in both wild-type and cerebellar microglia from 5xFAD animals, the high Aβ1-42 burden in the forebrain of 5xFAD animals likely underlies the exhaustion of microglial Aβ clearance capacity. These data may therefore explain why Aβ plaque formation has never been described in wild-type mice, and point to a beneficial role of microglia in AD pathology. We also describe a new method to study Aβ plaque formation in a cell culture setting.
authors.affiliation: Department of Psychiatry and Psychotherapy, Freiburg, Germany.
authors.forename: Sabine
authors.initials: S
authors.lastname: Hellwig
authors.affiliation: Department of Psychiatry and Psychotherapy, Freiburg, Germany.
authors.forename: Annette
authors.initials: A
authors.lastname: Masuch
authors.affiliation: Department of Neuroanatomy, Freiburg, Germany.
authors.forename: Sigrun
authors.initials: S
authors.lastname: Nestel
authors.affiliation: Department of Neurology, University of Freiburg, Freiburg, Germany.
authors.forename: Natalie
authors.initials: N
authors.lastname: Katzmarski
authors.affiliation: Department of Neurology, University of Freiburg, Freiburg, Germany.
authors.forename: Melanie
authors.initials: M
authors.lastname: Meyer-Luehmann
authors.affiliation: Department of Psychiatry and Psychotherapy, Freiburg, Germany.|Department of Neuroscience, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: Knut
authors.initials: K
authors.lastname: Biber
mesh_terms: D000367:Age Factors; D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology* / Q000517:prevention & control; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D001692:Biological Transport; D004195:Disease Models, Animal; D060467:Disease Resistance / Q000502:physiology; D005260:Female; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology* / Q000648:ultrastructure; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D017628:Microglia / Q000378:metabolism / Q000473:pathology* / Q000648:ultrastructure; D008867:Microtomy; D010446:Peptide Fragments / Q000378:metabolism*; D058225:Plaque, Amyloid / Q000378:metabolism / Q000473:pathology* / Q000517:prevention & control; D016548:Prosencephalon / Q000378:metabolism / Q000473:pathology* / Q000648:ultrastructure; D046509:Tissue Culture Techniques
chemical_list: D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42)