Objectives: A great deal of research has been conducted into the possible involvement of neurotrophins such as brain-derived neurotrophic factor (BDNF) in the pathogenesis of Alzheimer’s disease (AD). We hypothesized that lower BDNF serum levels may be associated with cognitive decline. To test this hypothesis, we examined the differences in the serum BDNF levels in patients with AD and mild cognitive impairment (MCI) and normal controls. Method: We enrolled 56 subjects with AD, 29 subjects with MCI, and 24 healthy control subjects in the study. A total of 109 subjects agreed to blood sampling to evaluate serum BDNF levels. Serum levels of BDNF were measured using an enzyme-linked immunosorbent assay (ELISA) method. Results: The MCI group had higher BDNF levels as compared to the AD group (p=0.027). However, there were no significant differences between either the AD group or the MCI group and the control group. A significant correlation was observed between MMSE-K score and serum BDNF level. However, BDNF serum concentrations did not significantly correlate with age or level of education in the AD, MCI, and control groups. Conclusion: Our data suggest that BDNF serum levels are increased in subjects with MCI, supporting the hypothesis of an upregulation of BDNF in preclinical stages. BDNF levels might be involved in the pathophysiology of cognitive decline in elderly people.