Mouse Wild Type and APP transgenic (Tg2576) hippocampus and response to LXR Agonist

The amyloidogenic processing of APP to A-beta is known to play a central role in Alzheimer’s disease pathogenesis. Despite this, however, the physiological role of APP and its processing still remains elusive. In the current study we utilzed a transcriptional profiling approach, to determine the pathways that may become dysregulated in the brains of APPswe transgenic mice (Tg2576). As many pathways linked to Alzheimer’s disease are also linked to cholesterol metabolism, we also treated the Tg2576 mice with LXR agonist TO901317, to determine the effects of LXR agonists on the hippocampal transcriptome of Tg2576 mice. We used microarrays to identify gene expression modulated in hippocampus of transgenic TG2576 mice that express human APP containing the Swedish mutation and the transcriptional responses to treatment with an LXR agonist. 50 mg/kg of TO901317 was administered once per day for 7 days to 20 weeks old Tg2576 mice or non-transgenic littermates by oral gavage in 2% Tween 80 and 0.5% sodium carboxymethylcellulose. Control animals were dosed with vehicle. One hour after the final dose, the animals were sacrificed, saline perfused and the brains extracted. Each brain was hemisected and the hippocampus dissected. The right hippocampus were processed for RNA extraction and hybridized to the MOE430 2.0 array.