title: Transgenic expression of the amyloid-beta precursor protein-intracellular domain does not induce Alzheimer's Disease-like traits in vivo.
abstract: BACKGROUND
  Regulated intramembranous proteolysis of the amyloid-beta precursor protein by the gamma-secretase yields amyloid-beta, which is the major component of the amyloid plaques found in Alzheimer's disease (AD), and the APP intracellular domain (AID). In vitro studies have involved AID in apoptosis and gene transcription. In vivo studies, which utilize transgenic mice expressing AID in the forebrain, only support a role for AID in apoptosis but not gene transcription.
  
  
  RESULTS
  Here, we have further characterized several lines of AID transgenic mice by crossing them with human Tau-bearing mice, to determine whether over-expression of AID in the forebrain provokes AD-like pathologic features in this background. We have found no evidence that AID overexpression induces AD-like characteristics, such as activation of GSK-3beta, hyperphosphorylation of Tau and formation of neurofibrillary pathology.
  
  
  CONCLUSIONS
  Overall, these data suggest that AID transgenic mice do not represent a model that reproduces the overt biochemical and anatomo-pathologic lesions observed in AD patients. They can still be a valuable tool to understand the role of AID in enhancing the cell sensitivity to apoptotic stimuli, whose pathways still need to be characterized.
authors.affiliation: The Litwin-Zucker Research Center for the Study of Alzheimer's Disease, The Feinstein Institute for Medical Research, North Shore-Long Island Jewish Health System, Manhasset, New York, United States of America. lgiliberto@nshs.edu
authors.forename: Luca
authors.initials: L
authors.lastname: Giliberto
authors.forename: Cristina
authors.initials: C
authors.lastname: d'Abramo
authors.forename: Christopher Michael
authors.initials: CM
authors.lastname: Acker
authors.forename: Peter
authors.initials: P
authors.lastname: Davies
authors.forename: Luciano
authors.initials: L
authors.lastname: D'Adamio
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D015153:Blotting, Western; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D008822:Mice, Transgenic; D010766:Phosphorylation; D016548:Prosencephalon / Q000378:metabolism / Q000473:pathology; D016875:tau Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D016564:Amyloid beta-Protein Precursor; D016875:tau Proteins