title: Increased occurrence of protein kinase CK2 in astrocytes in Alzheimer's disease pathology.
abstract: BACKGROUND
  Alzheimer's disease (AD) is the most common neurodegenerative disease. In addition to the occurrence of amyloid deposits and widespread tau pathology, AD is associated with a neuroinflammatory response characterized by the activation of microglia and astrocytes. Protein kinase 2 (CK2, former casein kinase II) is involved in a wide variety of cellular processes. Previous studies on CK2 in AD showed controversial results, and the involvement of CK2 in neuroinflammation in AD remains elusive.
  
  
  METHODS
  In this study, we used immunohistochemical and immunofluorescent staining methods to investigate the localization of CK2 in the hippocampus and temporal cortex of patients with AD and non-demented controls. We compared protein levels with Western blotting analysis, and we investigated CK2 activity in human U373 astrocytoma cells and human primary adult astrocytes stimulated with IL-1β or TNF-α.
  
  
  RESULTS
  We report increased levels of CK2 in the hippocampus and temporal cortex of AD patients compared to non-demented controls. Immunohistochemical analysis shows CK2 immunoreactivity in astrocytes in AD and control cases. In AD, the presence of CK2 immunoreactive astrocytes is increased. CK2 immunopositive astrocytes are associated with amyloid deposits, suggesting an involvement of CK2 in the neuroinflammatory response. In U373 cells and human primary astrocytes, the selective CK2 inhibitor CX-4945 shows a dose-dependent reduction of the IL-1β or TNF-α induced MCP-1 and IL-6 secretion.
  
  
  CONCLUSIONS
  This data suggests that CK2 in astrocytes is involved in the neuroinflammatory response in AD. The reduction in pro-inflammatory cytokine secretion by human astrocytes using the selective CK2 inhibitor CX-4945 indicates that CK2 could be a potential target to modulate neuroinflammation in AD.
authors.affiliation: Alzheimer center & Department of Neurology, Neuroscience Campus Amsterdam, VU University Medical Center, De Boelelaan 1118, 1081 HZ, Amsterdam, The Netherlands. a.rosenberger@vumc.nl.|Department of Pathology, Neuroscience Campus Amsterdam, VU University Medical Center, De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands. a.rosenberger@vumc.nl.
authors.forename: Andrea F N
authors.initials: AF
authors.lastname: Rosenberger
authors.affiliation: Department of Pathology, Neuroscience Campus Amsterdam, VU University Medical Center, De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands. tjadomorrema@hotmail.com.
authors.forename: Tjado H J
authors.initials: TH
authors.lastname: Morrema
authors.affiliation: Department of Pathology, Neuroscience Campus Amsterdam, VU University Medical Center, De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands. w.gerritsen@vumc.nl.
authors.forename: Wouter H
authors.initials: WH
authors.lastname: Gerritsen
authors.affiliation: Department of Pathology, Neuroscience Campus Amsterdam, VU University Medical Center, De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands. es.vanhaastert@vumc.nl.
authors.forename: Elise S
authors.initials: ES
authors.lastname: van Haastert
authors.affiliation: Department of Pathology, Neuroscience Campus Amsterdam, VU University Medical Center, De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands. hripsimesnkhchyan@yandex.com.
authors.forename: Hripsime
authors.initials: H
authors.lastname: Snkhchyan
authors.affiliation: PamGene International BV, Wolvenhoek 10, 5211 HH, 's-Hertogenbosch, The Netherlands. rhilhorst@pamgene.com.
authors.forename: Riet
authors.initials: R
authors.lastname: Hilhorst
authors.affiliation: Department of Pathology, Neuroscience Campus Amsterdam, VU University Medical Center, De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands. jm.rozemuller@vumc.nl.
authors.forename: Annemieke J M
authors.initials: AJ
authors.lastname: Rozemuller
authors.affiliation: Alzheimer center & Department of Neurology, Neuroscience Campus Amsterdam, VU University Medical Center, De Boelelaan 1118, 1081 HZ, Amsterdam, The Netherlands. p.scheltens@vumc.nl.
authors.forename: Philip
authors.initials: P
authors.lastname: Scheltens
authors.affiliation: Department of Pathology, Neuroscience Campus Amsterdam, VU University Medical Center, De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands. s.m.vander.vies@vu.nl.
authors.forename: Saskia M
authors.initials: SM
authors.lastname: van der Vies
authors.affiliation: Department of Pathology, Neuroscience Campus Amsterdam, VU University Medical Center, De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands. JJM.Hoozemans@vumc.nl.
authors.forename: Jeroen J M
authors.initials: JJ
authors.lastname: Hoozemans
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000473:pathology*; D000682:Amyloid / Q000378:metabolism; D001253:Astrocytes / Q000187:drug effects / Q000201:enzymology*; D001808:Blood Vessels / Q000378:metabolism / Q000473:pathology; D001921:Brain / Q000473:pathology*; D047390:Casein Kinase II / Q000378:metabolism; D002478:Cells, Cultured; D016207:Cytokines / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D009287:Naphthyridines / Q000494:pharmacology; D010619:Phenazines
chemical_list: D000682:Amyloid; D016207:Cytokines; D004791:Enzyme Inhibitors; D005904:Glial Fibrillary Acidic Protein; D009287:Naphthyridines; D010619:Phenazines; C555142:silmitasertib; C570325:CSNK2A1 protein, human; D047390:Casein Kinase II