Objective To investigate the correlation between serum lipids and expression levels of β-Amyloid protein (Aβ) and Tau in brain, and determine the intervention effect of medium-chain fatty acid (MCFA) in APP/PS1 mice, so as to provide a theoretical basis for exploring the mechanism of MCFA in the prevention and treatment of Alzheimer′s disease (AD). Methods Seventeen 4-week-old APP/PS1 transgenic mice were randomly divided into MCFA group (n=9) and long-chain fatty acid (LCFA) group (n=8), and 9 littermates of negative wild-type mice served as wide type (WT) group. Mice in each group were fed with diets prepared by different fatty acids until they were 36 weeks old, then the blood samples were collected to measure the serum lipids, including total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and the brain tissues were harvested to detect the expression levels of Aβ precursor protein (APP), Aβ and Tau protein in the cerebral cortex and hippocampus. SPSS statistics 22.0 was used for statistical analysis. Data comparison between the two groups was performed using student′s t test for measurement data. Pearson correlation analysis was used to analyze the correlation between blood lipids and the protein levels of Aβ and Tau. Results The serum levels of TC and TG and the protein levels of Aβ and Tau in the cerebral cortex and hippocampus were significantly lower in the MCFA group than the LCFA group (P<0.01). Correlation analysis indicated that serum TG was positively correlated with the Aβ level in the cortex(r=0.399; P<0.05), while serum TC was positively correlated with the expression level of Aβ in both cortex and hippocampus (r=0.715,0.748; P<0.01), and with the expression level of Tau in the hippocampus (r=0.603; P<0.05). Conclusion MCFA reduces Aβ deposition and Tau phosphorylation in the brain probably through regulating lipid metabolism, especially decreasing TC level in APP/PS1 transgenic mice, and thus plays a role in the prevention and treatment of AD.