Objective To provide a basis for clinical diagnosis, a serum metabonomic dynamic study was carried out on the Tg2576 mouse model at different stages of Alzheimer's disease (AD) whose pathological progress is similar to that of human AD patients. Methods Serum samples of Tg2576 mice were collected at the early(6 months) and late(12 months) stages of Alzheimer's disease.The ¹H NMR spectra of the serum samples were collected and the metabolic characteristics were analyzed by multivariate analysis.Results Significant differences in serum metabonomics were found in the transgenic Tg2576 mice and C57 mice at 6 and 12 months of age, and there were significant metabolic changes in Tg2576 mice at different stages of Alzheimer's disease. Compared with C57 mice, the Tg2576 mice at early stage of Alzheimer's disease showed higher levels of serum lactate,myo-inositol and amino acids (such as leucine, isoleucine, alanine), and lower levels of lipids, choline, phosphorylcholine, glycerol phosphorglcholine, betaine, glycine and glucose.At the late stage of Alzheimer's disease, the transgenic Tg2576 mice had higher levels of lactate, myo-inositol and alanine,while the serum levels of lipids, choline, phosphorylcholine, glycerophosphorylcholine, betaine, and glycine continued to drop. Meanwhile glutamine and creatine levels started to decline. By comparing the early and late serum metabolites of Alzheimer's disease, serum metabonomic profiles of the late stage of Alzheimer's disease indicated an up-regulation of lactate, myo-inositol and alanine, and a down-regulation of lipids,choline, phosphorylcholine and glycerophosphorylcholinelevels.Moreover, the levels of lactate, lipids, choline, phosphorylcholine and glycerophosphorylcholine showed statistical significance at the early stage of AD, and they were closely correlated with the severity of Alzheimer's disease. Conclusions The above results show that the changes of lactate, myo-inositol and alanine are positively-correlated with the development of AD, while the serum levels of lipids, choline, phosphorylcholine and glycerophosphorylcholine are inversely-proportional to the severity of AD. These metabolites are dynamically and progressively changed along with the disease progression, which hopefully may serve as early metabolic markers for the diagnosis of AD in clinical practice.