Abstract: Amyloid beta (Aβ) monomers aggregate to form fibrils and amyloid plaques, which is one of the important mechanisms in the pathogenesis of Alzheimer's disease (AD). Since the Aβ1-42 aggregation has prominent role in plaque formation, which eventually lead to the patient's brain lesions and cognitive impairment, an increasing number of studies have been devoted to reduce Aβ aggregation process to slow down AD progression. Since the diphenylalanine (FF) sequence is critical for amyloid aggregation, and it has been shown that magnetic fields can affect the alignment of peptide assembly due to the diamagnetic anisotropy of aromatic rings, here we used a moderate-intensity rotating magnetic field (RMF), to explore its effect in Aβ aggregation and AD pathogenesis. Our data show that RMF can directly inhibit Aβ amyloid fibril formation and reduced Aβ-induced cytotoxicity on neural cells in vitro. Using the AD mice model APP/PS1, we found that the RMF can restore their motor ability to the healthy control level. Their cognitive impairments, including exploration and spatial memory abilities were also significantly alleviated. Tissue examinations reveal that RMF has reduced amyloid plaque accumulation, attenuated microglial activation and reduced oxidative stress in the APP/PS1 mice brain. Therefore, our data demonstrate the great potential of RMF to be developed as a non-invasive, high penetration physical approach to be applied in the treatment of AD.