Background: Alzheimer’s disease (AD) is a non-reversible and deleterious neurodegenerative disease. The brains of AD patients are characterized by pathological features, including amyloid-?(A?) senile plaques, which lead to damage and atrophy to neuronal structures. ?-site amyloid precursor protein cleaving enzyme 1(BACE1), is the key protein involved in A? peptide generation. Previous studies indicated that BACE1 initially cleaves the amyloid precursor protein(APP) and may subsequently interfere with physiological functions of proteins such as PKA, which is recognized to be closely associated with long-term potentiation(LTP), and could effectively ameliorate cognitive impairments. Electro acupuncture has reported to mitigate cognitive deficits of AD mice. The aim of this study was to reveal the underlying mechanism of electro acupuncture treatment to memory and learning dysfunction of AD mice.

Methods: 20 APP/PS1mice were randomly divided into Model(M) group and Electro acupuncture (EA) group, C57BL/6 mice were used for normal control(C) group, n=10 in each group. After fifteen days of intervention, Morris water maze test was performed to observe the behavior changes in each group. The expression of BACE1, APP and p-PKA were detected by immunofluorescence, Immunohistochemistry and western blot.

Results: Compared with M group, the escape latency of EA group significantly declined(P<0.01), and the percentage of time spent in target quadrant showed an obvious increase(P<0.05). Meanwhile, the EA group presented faster swimming speed (P<0.05) and higher platform crossing frequency(P<0.05). The immunofluorescence, Immunohistochemistry and western blot detection revealed that EA group had lower expression of BACE1, APP(P<0.05) and higher activation of PKA(P<0.05) than that in M group.

Conclusions: Taken together, the results suggest that EA could down-regulate APP and BACE1 expression and activate PKA pathway to ameliorate memory dysfunction of APP/PS1 mice. The findings could serve as a preliminary proof for EA treatment as a complementary replacement for AD pathogenesis.