title: Reduced β-amyloid pathology in an APP transgenic mouse model of Alzheimer's disease lacking functional B and T cells.
abstract: BACKGROUND
  In Alzheimer's disease, accumulation and pathological aggregation of amyloid β-peptide is accompanied by the induction of complex immune responses, which have been attributed both beneficial and detrimental properties. Such responses implicate various cell types of the innate and adaptive arm of the immunesystem, both inside the central nervous system, and in the periphery. To investigate the role of the adaptive immune system in brain β-amyloidosis, PSAPP transgenic mice, an established mouse model of Alzheimer's disease, were crossbred with the recombination activating gene-2 knockout (Rag2 ko) mice lacking functional B and T cells. In a second experimental paradigm, aged PSAPP mice were reconstituted with bone marrow cells from either Rag2 ko or wildtype control mice.
  
  
  RESULTS
  Analyses from both experimental approaches revealed reduced β-amyloid pathology and decreased brain amyloid β-peptide levels in PSAPP mice lacking functional adaptive immune cells. The decrease in brain β-amyloid pathology was associated with enhanced microgliosis and increased phagocytosis of amyloid β-peptide aggregates.
  
  
  CONCLUSIONS
  The results of this study demonstrate an impact of the adaptive immunity on cerebral β-amyloid pathology in vivo and suggest an influence on microglia-mediated amyloid β-peptide clearance as a possible underlying mechanism.
authors.affiliation: Division of Psychiatry Research, University of Zurich, Wagistrasse 12, 8952, Schlieren, Switzerland.|Neuroscience Center Zurich (ZNZ), Wintherthurerstrasse 190, 8057, Zurich, Switzerland.
authors.forename: Claudia
authors.initials: C
authors.lastname: Späni
authors.affiliation: Department of Neurology, Section of Neuroimmunology and MS Research, University Hospital Zurich, 8091, Zurich, Switzerland.|Neuroscience Center Zurich (ZNZ), Wintherthurerstrasse 190, 8057, Zurich, Switzerland.
authors.forename: Tobias
authors.initials: T
authors.lastname: Suter
authors.affiliation: Division of Psychiatry Research, University of Zurich, Wagistrasse 12, 8952, Schlieren, Switzerland.|Neuroscience Center Zurich (ZNZ), Wintherthurerstrasse 190, 8057, Zurich, Switzerland.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Derungs
authors.affiliation: Division of Psychiatry Research, University of Zurich, Wagistrasse 12, 8952, Schlieren, Switzerland.|Neuroscience Center Zurich (ZNZ), Wintherthurerstrasse 190, 8057, Zurich, Switzerland.
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Ferretti
authors.affiliation: Division of Psychiatry Research, University of Zurich, Wagistrasse 12, 8952, Schlieren, Switzerland.
authors.forename: Tobias
authors.initials: T
authors.lastname: Welt
authors.affiliation: Division of Psychiatry Research, University of Zurich, Wagistrasse 12, 8952, Schlieren, Switzerland.|Neuroscience Center Zurich (ZNZ), Wintherthurerstrasse 190, 8057, Zurich, Switzerland.
authors.forename: Fabian
authors.initials: F
authors.lastname: Wirth
authors.affiliation: Division of Psychiatry Research, University of Zurich, Wagistrasse 12, 8952, Schlieren, Switzerland.|Neuroscience Center Zurich (ZNZ), Wintherthurerstrasse 190, 8057, Zurich, Switzerland.
authors.forename: Christoph
authors.initials: C
authors.lastname: Gericke
authors.affiliation: Division of Psychiatry Research, University of Zurich, Wagistrasse 12, 8952, Schlieren, Switzerland.|Neuroscience Center Zurich (ZNZ), Wintherthurerstrasse 190, 8057, Zurich, Switzerland.
authors.forename: Roger M
authors.initials: RM
authors.lastname: Nitsch
authors.affiliation: Division of Psychiatry Research, University of Zurich, Wagistrasse 12, 8952, Schlieren, Switzerland. luka.kulic@bli.uzh.ch.|Zurich Center for Integrative Human Physiology (ZIHP), University of Zurich, Rämistrasse 71, 8006, Zurich, Switzerland. luka.kulic@bli.uzh.ch.|Neuroscience Center Zurich (ZNZ), Wintherthurerstrasse 190, 8057, Zurich, Switzerland. luka.kulic@bli.uzh.ch.
authors.forename: Luka
authors.initials: L
authors.lastname: Kulic
mesh_terms: D019264:Adoptive Transfer; D000544:Alzheimer Disease / Q000235:genetics* / Q000473:pathology* / Q000503:physiopathology; D016229:Amyloid beta-Peptides / Q000235:genetics / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics*; D000818:Animals; D001402:B-Lymphocytes / Q000473:pathology*; D016207:Cytokines / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics; D004195:Disease Models, Animal; D005106:Exploratory Behavior / Q000502:physiology; D005260:Female; D006801:Humans; D008297:Male; D018782:Maze Learning / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010446:Peptide Fragments / Q000235:genetics / Q000378:metabolism*; D021641:Recognition, Psychology / Q000502:physiology; D013601:T-Lymphocytes / Q000473:pathology*
chemical_list: D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D016207:Cytokines; D004268:DNA-Binding Proteins; D010446:Peptide Fragments; C499308:Rag2 protein, mouse; C078639:amyloid beta-protein (1-38)