title: Amyloid deposition in APP23 mice is associated with the expression of cyclins in astrocytes but not in neurons.
abstract: Alzheimer's disease (AD) is a neurodegenerative disorder characterized by the intracellular accumulation of highly phosphorylated tau protein, the extracellular formation of amyloid plaques and a significant loss of neurons. Recent evidence suggests that neuronal death in AD involves an aborted attempt of cells to re-enter the cell cycle. To study the effect of amyloid deposits on cell cycle related events in vivo, the expression of cell cycle markers was examined by immunohistochemistry in amyloid precursor protein (APP) transgenic mice (APP23 mice, Swedish double mutation). Abeta deposition in APP23 mice is associated with prominent gliosis that is characterized by an astrocytic expression of cyclins D1, E and B1 as well as the nuclear translocation of cyclin-dependent protein kinase 4. However, amyloid plaque formation is not accompanied by significant changes in the neuronal expression of cyclins or cyclin-dependent kinase inhibitors. It is concluded, therefore, that in contrast to AD, amyloid pathology in APP23 mice is not associated with changes in the expression of cell cycle markers in neurons. The results support the assumption that the neuronal re-expression of cell cycle components in AD is not a consequence of Abeta formation and deposition.
authors.affiliation: Department of Neuroanatomy, Paul Flechsig Institute of Brain Research, University of Leipzig, Jahnallee 59, 04109, Leipzig, Germany. gaeru@medizin.uni-leipzig.de
authors.forename: Ulrich
authors.initials: U
authors.lastname: Gärtner
authors.forename: Martina K
authors.initials: MK
authors.lastname: Brückner
authors.forename: Sabine
authors.initials: S
authors.lastname: Krug
authors.forename: Stefanie
authors.initials: S
authors.lastname: Schmetsdorf
authors.forename: Matthias
authors.initials: M
authors.lastname: Staufenbiel
authors.forename: Thomas
authors.initials: T
authors.lastname: Arendt
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics / Q000503:physiopathology; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001253:Astrocytes / Q000378:metabolism*; D015153:Blotting, Western; D001921:Brain / Q000378:metabolism / Q000473:pathology; D002453:Cell Cycle / Q000502:physiology; D018844:Cyclin-Dependent Kinases / Q000378:metabolism; D016213:Cyclins / Q000096:biosynthesis*; D004195:Disease Models, Animal; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D008822:Mice, Transgenic; D009474:Neurons / Q000378:metabolism*; D021381:Protein Transport / Q000502:physiology
chemical_list: D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D016213:Cyclins; D018844:Cyclin-Dependent Kinases