Discrepancy of synaptic and microtubular protein phosphorylation in the hippocampus of APP/PS1 and MAPTxP301S transgenic mice at the early stage of Alzheimer's disease

Alzheimer's disease (AD) is the most common neurodegenerative disorder, and is caused by multiple pathological factors, such as the overproduction of ss- amyloid (A ss) 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. Thus in this study, a quantitative phosphoproteomics analysis was performed to evaluate global protein phosphorylation in the hippocampus of A ss overexpressing APP/PS1 transgenic mice and tau overexpressing MAPTxP301S transgenic mice, two in vivo AD model systems. These animals, up to ten weeks old, do not exhibit cognitive dysfunctions and are widely used to simulate early-stage AD patients. The number of differentially phosphorylated proteins ( DPPs) was greater for APP/PS1 transgenic mice than for MAPTxP301S transgenic mice. The function of the DPPs in APP/ PS1 transgenic mice was mainly related to synapses, while the function of the DPPs in MAPTxP301S transgenic mice was mainly related to microtubules. In addition, an AD core network was established including seven phosphoproteins differentially expressed in both animal models, and the function of this core network was related to synapses and oxidative stress. The results of this study suggest that A ss and tau 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.