Objective:To explore the potential application value of photobiomodulation and drug combination therapy in the treatment of Alzheimer's disease (AD).Methods:Twenty-five APPswe/PS1dE9 double transgenic mice were randomly divided into model control group, donepezil hydrochloride (DH) group, DH+10 Hz group, DH+20 Hz group, and DH+40 Hz group ( n=5); and 5 C57BL/6J mice were selected as blank control group. Mice in the DH group, DH+10 Hz group, DH+20 Hz group, and DH+40 Hz group were given intragastric administration of DH (1.3 mg/[kg·d] for 4 weeks). The mice in the DH+10 Hz group, DH+20 Hz group, and DH+40 Hz group were irradiated with 1050 nm near-infrared light at 10 Hz, 20 Hz and 40 Hz frequencies for 6 min/d for 4 consecutive weeks. After all these treatments, Morris water maze was used to detect the behavioral cognitive ability of mice in each group; Congo red staining was used to detect the amyloid deposition in hippocampal CA1 area; and ELISA was used to detect the protein expression levels of amyloid protein (Aβ) 1-40 and Aβ 1-42 in the hippocampus. Results:(1) As compared with that in the model control group, the escape latency of mice in the DH+40 Hz group was significantly shortened since the 4 th d of navigation test, and that in the DH group was significantly shortened since the 5 th d of navigation test ( P<0.05); that in the DH+40 Hz group was obviously shortened as compared with that in the DH group without significant difference ( P>0.05). As compared with the those in the model control group, the times of crossing the primary platform of mice in the DH group and DH+40 Hz group were singifcantly increased ( P<0.05), and those in the DH+40 Hz group were similar to those in the DH group. (2) DH+40 Hz group showed scattered brick-red dotted patches, the staining depth and distribution range were obviously smaller than those in the model control group, and the nuclear structure arrangement was more orderly than that in the model control group; the staining depth and number of brick red patches in the DH+40 Hz group were smaller than those in the DH group. (3) The concentrations of Aβ 1-40 and Aβ 1-42 in the hippocampal tissue homogenate of DH+40 Hz group were significantly decreased as compared with those in the model control group ( P<0.05). As compared with those in the DH group, the concentrations of Aβ 1-40 and Aβ 1-42 in hippocampal tissue homogenate of DH+40 Hz group were decreased without significant difference ( P>0.05). Conclusion:The combined treatment strategy of 40 Hz 1050 nm near-infrared light and DH may have the potential to improve the behavioral cognition of AD mice and moderately reduce the deposition of Aβ in the brain tissues.