Transgenic expression of the amyloid-β precursor protein-intracellular domain does not induce Alzheimer's disease-like traits in vivo

Background: Regulated intramembranous proteolysis of the amyloid-β precursor protein by the γ-secretase yields amyloidβ, 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. Methodology/Principal Findings: 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-3β, hyperphosphorylation of Tau and formation of neurofibrillary pathology. Conclusions/Significance: 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.