PSEN1 and Alzheimer disease: In another AD mice model (bearing App(swe) and Psen1 dE9 transgenes), transgenic over-expression of SIRT1 in the brain markedly reduced amyloid plaque formation, gliosis and decline in learning and memory capabilities, while brain SIRT1 specific knock-out had greatly attenuated lifespan likely due to juvenile onset of an AD-like disease (Donmez et al., 2010).