Many researches have been trying to find the potential biomarkers for Alzheimer's disease (AD). We hereby used the proteomics method to search for protein expression differences in the serum between AD patients and controls. We enrolled 59 AD patients and 74 age- and sex-matched controls in this study. Ten AD patients and 10 controls were selected for proteomic analysis. Apolipoprotein A-I (ApoA-I) was found to have a lower expression in the AD group by a proteomics two-dimensional gel electrophoresis study. We further measured the serum ApoA-I level which was significantly lower in the AD patients (112.29 +/- 21.33 mg/dl) in comparison to the controls (144.53 +/- 19.91 mg/dl; p < 0.0002). Lower serum ApoA-I levels might be a potential biomarker for AD.