APP and Alzheimer disease: Most prior studies on activation of the HIF pathway on AD have predominately been carried out in the APP/PS1 mice by environmental hypoxia, which has often been very severe (down to 9% O2), having cycles of hypoxia and normoxia when a reperfusion injury is likely to occur, and the length of the intervention varying from 14 to 60 days (11, 12, 13, 14, 15, 16, 17).