title: Microglia display modest phagocytic capacity for extracellular tau oligomers.
abstract: BACKGROUND
  Abnormal misfolded tau protein is a driving force of neurofibrillary degeneration in Alzheimer's disease. It has been shown that tau oligomers play a crucial role in the formation of intracellular neurofibrillary tangles. They are intermediates between soluble tau monomers and insoluble tau filaments and are suspected contributors to disease pathogenesis. Oligomeric tau can be released into the extracellular space and spread throughout the brain. This finding opens the question of whether brain macrophages or blood monocytes have the potential to phagocytose extracellular oligomeric tau.
  
  
  METHODS
  We have used stable rat primary microglial cells, rat peripheral monocytes-derived macrophages, BV2 microglial and TIB67 macrophage immortalized cell lines that were challenged by tau oligomers prepared by an in vitro aggregation reaction. The efficiency of cells to phagocytose oligomeric protein was evaluated with confocal microscopy. The ability to degrade tau protein was analyzed by immunoblotting.
  
  
  RESULTS
  Confocal microscopy analyses showed that macrophages were significantly more efficient in phagocytosing oligomerized tau proteins than microglial cells. In contrast to macrophages, microglia are able to degrade the internalized oligomeric tau only after stimulation with lipopolysaccharide (LPS).
  
  
  CONCLUSIONS
  Our data suggests that microglia may not be the principal phagocytic cells able to target extracellular oligomeric tau. We found that peripheral macrophages display a high potency for elimination of oligomeric tau and therefore could play an important role in the modulation of neurofibrillary pathology in Alzheimer's disease.
authors.forename: Petra
authors.initials: P
authors.lastname: Majerova
authors.forename: Monika
authors.initials: M
authors.lastname: Zilkova
authors.forename: Zuzana
authors.initials: Z
authors.lastname: Kazmerova
authors.forename: Andrej
authors.initials: A
authors.lastname: Kovac
authors.forename: Kristina
authors.initials: K
authors.lastname: Paholikova
authors.forename: Branislav
authors.initials: B
authors.lastname: Kovacech
authors.forename: Norbert
authors.initials: N
authors.lastname: Zilka
authors.forename: Michal
authors.initials: M
authors.lastname: Novak
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002478:Cells, Cultured; D005110:Extracellular Space / Q000378:metabolism; D006801:Humans; D008264:Macrophages / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000378:metabolism*; D046529:Microscopy, Electron, Transmission; D010587:Phagocytosis / Q000502:physiology*; D055503:Protein Multimerization; D051381:Rats; D017207:Rats, Sprague-Dawley; D016875:tau Proteins / Q000378:metabolism*
chemical_list: C054369:MAPT protein, human; D016875:tau Proteins