To investigate the effect of Aβ on mitochondrial dysfunction, cells stably transfected by human amyloid precursor protein 695 (APP) and cells stably co-transfected by familial Alzheimer’s disease (FAD)-linked Swedish mutant of APP695 gene plus ΔE9 deleted presenilin1 gene (swe. Δ9) were used to study the mitochondrial function. Swe. Δ9 cells showed more reduce in mitochondrial membrane potential, altered complexⅣ activity, mitochondrial membrane fluidity and ATP content. However, these parameters in APP cells were lower than those in N2a cells stably transfected with empty vector. The similar results were observed in transgenic mice. APP/PS1M146V/+ mice showed more reduced complexⅣ activity and ATP content than Tg2576 mice. These data indicated that the dose-dependent effect of Aβ on mitochondrial dysfunction.