title: Mechanisms of action of naturally occurring antibodies against β-amyloid on microglia.
abstract: BACKGROUND
  Naturally occurring autoantibodies against amyloid-β (nAbs-Aβ) have been shown to exert beneficial effects on transgenic Alzheimer's disease (AD) animals in vivo and on primary neurons in vitro. Not much is known about their effect on microglial cells. Our aim was to investigate the effect of nAbs-Aβ on amyloid-β (Aβ)-treated microglial cells in vitro with respect to cell viability, stress pathways, cytokine production and phagocytotic abilities and whether these effects can be conveyed to neurons.
  
  
  METHODS
  Primary microglial cells isolated from Swiss Webster mouse mesencephalons on embryonic day 13.5 were pretreated with nAbs-Aβ and then treated with Aβ oligomers. After 3 hours, phagocytosis as well as western blot analysis were evaluated to measure the amount of phagocytized Aβ. Cell viability was analyzed using an MTT assay 24 hours after treatment. Pro-inflammatory cytokines in the supernatants were analyzed with ELISAs and then we treated primary neuronal cells with these conditioned microglia supernatants. Twenty-four hours later we did a MTT assay of the treated neurons. We further investigated the effect of a single nAbs-Aβ administration on Tg2576 mice in vivo.
  
  
  RESULTS
  Upon co-administration of Aβ and nAbs-Aβ no change in microglia viability was observed. However, there was an increase in phosphorylated p38 protein level, an increase in the pro-inflammatory cytokines TNF-α and IL-6 and an increase in Aβ uptake by microglial cells. Treatment of primary neurons with conditioned microglia medium led to a 10% improvement in cell viability when nAbs-Aβ were co-administered compared to Aβ-treated cells alone. We were unable to detect changes in cytokine production in brain lysates of Tg2576 mice.
  
  
  CONCLUSIONS
  We provide evidence on the mechanism of action of nAbs-Aβ on microglia in vitro. Interestingly, our in vivo data indicate that nAbs-Aβ administration should be considered as a therapeutic strategy in AD, since there is no inflammatory reaction.
authors: Department of Neurology, Philipps-University of Marburg, Baldingerstraße 1, 35043, Marburg, Germany. dodel@med.uni-marburg.de
authors: Maike
authors: M
authors: Gold
authors: David
authors: D
authors: Mengel
authors: Stephan
authors: S
authors: Röskam
authors: Richard
authors: R
authors: Dodel
authors: Jan-Philipp
authors: JP
authors: Bach
mesh_terms: D016229:Amyloid beta-Peptides / Q000235:genetics / Q000276:immunology*; D000818:Animals; D001323:Autoantibodies / Q000008:administration & dosage / Q000502:physiology*; D002470:Cell Survival / Q000235:genetics / Q000276:immunology; D002478:Cells, Cultured; D006224:Cricetinae; D005260:Female; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D017628:Microglia / Q000276:immunology*
chemical_list: D016229:Amyloid beta-Peptides; D001323:Autoantibodies