title: Up-regulation of Synaptotagmin IV within amyloid plaque-associated dystrophic neurons in Tg2576 mouse model of Alzheimer's disease.
abstract: OBJECTIVE
  To investigate the involvement of the vesicular membrane trafficking regulator Synaptotagmin IV (Syt IV) in Alzheimer's disease pathogenesis and to define the cell types containing increased levels of Syt IV in the β-amyloid plaque vicinity.
  
  
  METHODS
  Syt IV protein levels in wild type (WT) and Tg2576 mice cortex were determined by Western blot analysis and immunohistochemistry. Co-localization studies using double immunofluorescence staining for Syt IV and markers for astrocytes (glial fibrillary acidic protein), microglia (major histocompatibility complex class II), neurons (neuronal specific nuclear protein), and neurites (neurofilaments) were performed in WT and Tg2576 mouse cerebral cortex.
  
  
  RESULTS
  Western blot analysis showed higher Syt IV levels in Tg2576 mice cortex than in WT cortex. Syt IV was found only in neurons. In plaque vicinity, Syt IV was up-regulated in dystrophic neurons. The Syt IV signal was not up-regulated in the neurons of Tg2576 mice cortex without plaques (resembling the pre-symptomatic conditions).
  
  
  CONCLUSIONS
  Syt IV up-regulation within dystrophic neurons probably reflects disrupted vesicular transport or/and impaired protein degradation occurring in Alzheimer's disease and is probably a consequence but not the cause of neuronal degeneration. Hence, Syt IV up-regulation and/or its accumulation in dystrophic neurons may have adverse effects on the survival of the affected neuron.
authors.affiliation: Gordana Glavan, Laboratory for Brain Research, Institute of Pathophysiology, Medical Faculty, Zaloska 4, Ljubljana 1000, Slovenia, gordana.glavan@mf.uni-lj.si.
authors.forename: Larisa
authors.initials: L
authors.lastname: Tratnjek
authors.forename: Marko
authors.initials: M
authors.lastname: Zivin
authors.forename: Gordana
authors.initials: G
authors.lastname: Glavan
mesh_terms: D000544:Alzheimer Disease / Q000209:etiology / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001253:Astrocytes / Q000737:chemistry; D015153:Blotting, Western; D002540:Cerebral Cortex / Q000737:chemistry; D004195:Disease Models, Animal; D005455:Fluorescent Antibody Technique; D007150:Immunohistochemistry; D051379:Mice; D008822:Mice, Transgenic; D009474:Neurons / Q000737:chemistry / Q000378:metabolism*; D058225:Plaque, Amyloid / Q000378:metabolism; D050857:Synaptotagmins / Q000032:analysis / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D050857:Synaptotagmins