Alzheimer's disease (AD) is a common human neurodegenerative disorder characterized by progressive deterioration of cognition and memory. Acupuncture at the Baihui (DU20) acupoint has long been used in China to clinically treat cognitive impairment. However, the precise mechanism underlying its neuroprotective effects remains to be elucidated. In the present study, electroacupuncture (EA) at the Baihui (DU20) acupoint was observed to markedly ameliorate cognitive impairments, reduce the aberrant overexpression of β-amyloid(1-42), and inhibit neuronal apoptosis in APP/PS1 mice. As brain-derived neurotrophic factor (BDNF) has been implicated in the pathogenesis of AD, the expression and processing of BDNF in APP/PS1 mice was investigated. EA at the Baihui (DU20) acupoint was indicated to significantly enhance the expression levels of mature BDNF and proBDNF in APP/PS1 mice. Furthermore, an increase in the BDNF/proBDNF ratio, upregulation of the expression levels of phosphorylated tropomyosin receptor kinase B and a decrease in the expression level of p75 neurotrophin receptor were also observed in the APP/PS1 mice. The present study demonstrates the efficacy of EA at the Baihui (DU20) acupoint in the treatment of cognitive impairments in APP/PS1 transgenic mice. The present study hypothesized that modulation of BDNF expression and processing may be the underlying mechanism by which stimulation of the Baihui (DU20) acupoint exerts its neuroprotective effect.