Abstract: Objective To investigate the effects of type 2 diabetes on learning and memory of APP/PS1/Tau triple transgenic (3×Tg) mice of Alzheimer’ s disease, and the protective mechanism of liraglutide (LIR) thereof. Methods One month old C57BL/6 mice were set to be control group (WT). One month old 3×Tg mice were divided into control group (Tg), liraglutide group (Tg+LIR), type 2 diabetes group (Tg+T2DM) and liraglutide treatment group (Tg+T2DM+LIR). The model of T2DM was established by feeding the high fat and sugar fodder, and then injecting streptozotocin (STZ) in mice, making sure the fasting blood glucose was more than 7 mmol/L. Then the subcutaneous injection of LIR was administered for 2 months. The values of body weight and fasting blood glucose were detected at age of 5-month. Morris water maze was applied to evaluate the spatial learning and memory ability. Western blotting assay was used to measure the levels of phosphorylated Tau, neurofilament (NFs) and insulin receptor substrates. ELISA was used to detect the human Aβ 42 to evaluate the effect of LIR on -amyloid. Results LIR can reduce body weight and blood glucose, can alleviate spatial learning and memory damaging caused by T2DM, and also can improve phosphorylated Tau levels, NFs and insulin receptor substrates caused by
T2DM, and finally can reduce the deposition of β-amyloid of 3×Tg mice. Conclusion T2DM can aggravate symptoms of AD in 3×Tg mice, and LIR has a protective effect on it.

Key words: Alzheimer disease, diabetes mellitus, type 2, amyloid beta-protein, insulin resistance, liraglutide, Tau, insulin receptor substrate, neurofilaments