title: The Effect of Aβ₁₋₄₂ Oligomers on APP Processing and Aβ₁₋₄₀ Generation in Cultured U-373 Astrocytes.
abstract: BACKGROUND
  Amyloid-β (Aβ) peptides are a family of proteins that are considered to be a principal aspect of Alzheimer's disease (AD), the most common cause of senile dementia affecting elderly individuals. These peptides result from the proteolytic processing of amyloid precursor protein (APP) by sequential cleavage mediated via β- and x03B3;-secretases. Evidence suggests that an overproduction and/or a lack of degradation may increase brain Aβ levels which, in turn, contribute to neuronal loss and development of AD.
  
  
  OBJECTIVE
  In this study, we seek to determine what effect Aβ has on APP processing in cultured astrocytes.
  
  
  METHODS
  Using the human astrocytoma cell line U-373, we investigated the effects induced by oligomeric Aβ1-42 treatment on the cellular levels/expression of APP and its products, C-terminal fragments αCTF and βCTF, and Aβ1-40. In conjunction with these experiments, we examined the relative levels and activity of β- and x03B3;-secretases in Aβ-treated astrocytes.
  
  
  RESULTS
  We report here that Aβ1-42 treatment of astrocytes increased the expression of APP and its cleaved products including Aβ1-40 in a time-dependent manner.
  
  
  CONCLUSIONS
  These results suggest that activated astrocytes can contribute to the development of AD by enhancing levels and processing of APP leading to an increased production/secretion of Aβ-related peptides.
authors.affiliation: Department of Psychiatry, University of Alberta, Edmonton, Alta., Canada.
authors.forename: Dimitar
authors.initials: D
authors.lastname: Ourdev
authors.forename: Bahram V
authors.initials: BV
authors.lastname: Foroutanpay
authors.forename: Yanlin
authors.initials: Y
authors.lastname: Wang
authors.forename: Satyabrata
authors.initials: S
authors.lastname: Kar
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism; D053829:Amyloid Precursor Protein Secretases / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D001253:Astrocytes / Q000378:metabolism*; D002478:Cells, Cultured; D006801:Humans; D010446:Peptide Fragments / Q000378:metabolism*
chemical_list: D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40); C075222:amyloid beta-protein (1-42); D053829:Amyloid Precursor Protein Secretases