Alzheimer’s disease (AD) is the most common neurodegenerative disorder caused by multiple pathological factors such as the overproduction of β-amyloid (Aβ) and the hyperphosphorylation of tau. However, there is limited knowledge of the mechanisms underlying AD pathogenesis and no effective biomarker for the early diagnosis of this disorder. In this study, we performed a quantitative phosphoproteomic analysis for the evaluation of global protein phosphorylation in the hippocampus of Aβ overexpression APP/PS1 transgenic mice, and tau overexpression MAPT×P301S transgenic mice, respectively. These AD mice at ten-week-old did not exhibit cognitive dysfunction and were widely used to simulate AD patients at the early stage. The number of differentially phosphorylated proteins (DPPs) was greater in APP/PS1 transgenic mice than those of MAPT×P301S transgenic mice. And the function of DPPs in APP/PS1 transgenic mice was mainly related to synapse, while the function of DPPs in MAPT×P301S transgenic mice was mainly related to microtubule. In addition, an AD core network containing 7 phosphoproteins differentially expressed in both animal models was established, and the function of this core network related to synapse and oxidative stress. All these results indicated that Aβ and tau might induce different protein phosphorylation profiles in the early stage of AD, leading to the dysfunctions in synapses and microtubule, respectively. And the detection of same DPPs in these animal models might be used for early AD diagnosis.