High‐frequency transcranial magnetic stimulation protects APP/PS1 mice against Alzheimer’s disease progress by reducing APOE and enhancing autophagy

INTRODUCTION: The repetitive transcranial magnetic stimulation (rTMS) has clinically wide application prospect of psychiatry and neuroscience, for its painless, noninvasive, and high efficiency. So far, rTMS has been used in the treatment of Alzheimer's disease (AD) but the underlying mechanism is not clear. METHODS AND RESULTS: The APP/PS1 mice at 3‐month‐old were treated by 5 Hz high‐frequency (HF) rTMS for two weeks. After rTMS treatment, the AD‐like cognitive impairments of APP/PS1 mice were investigated subsequently, and molecular mechanisms underlying was further explored. The study showed that the 2‐week rTMS at 5Hz frequency improved cognitive impairments and AD‐like pathology (including a decrease in p‐Tau, APP, Aβ, and PP2A expression) of APP/PS1 mice. Although BDNF‐TrkB signaling was significantly enhanced, no differences of SYN, PSD95 and p‐AKT were observed in the brain of APP/PS1 mice. On the contrary, the LC3Ⅱ/LC3Ⅰ ratio was elevated with a significant reduction of ApoE and p62 in mice. CONCLUSIONS: rTMS exerts a potentially protective role in the prevention and treatment of AD by reducing ApoE expression and promoting autophagic flux, which provides a new insight into the mechanism of rTMS.