Investigating the effects of 40 Hz sound stimulation on Alzheimer's disease pathways: Modulation of amyloid-β42 secretion, tau phosphorylation, phagocytosis, and autophagy

Background Alzheimer's disease (AD) is the main cause of dementia in an aging society. Previous studies have demonstrated that non-invasive light flicker and sound with gamma frequency oscillations can modulate AD-related pathology in AD mice, potentially improving patient outcomes. However, the molecular mechanism by which sound with gamma frequency oscillations inhibits the expression of amyloid-β 1–42 (Aβ 42 ) and the phosphorylation of tau, and modulating cell autophagy in nerve cells are still unclear. Objective This study aimed to explore the molecular effects of 40 Hz sound stimulation on AD-related pathways in a cellular model. Methods We designed a 40 Hz stimulating sound (H + multi-frequency audio) for this study, and cells were exposed to H + multi-frequency audio. The concentration of Aβ 42 was quantified by enzyme-linked immunosorbent assay. Protein levels were examined by western blotting. Phagocytosis was examined by confocal microscopy and phagocytic analysis. Results First, we found that exposure to the 40 Hz stimulating sound inhibited the secretion of Aβ 42 by activating the AβPP/ADAM10 pathway and suppressing the AβPP/BACE1 pathway. Second, 40 Hz stimulating sound inhibited tau phosphorylation at Thr181 through the inactivation of the Akt/mTOR pathway. Third, 40 Hz stimulating sound enhanced the phagocytosis and autophagy of Aβ 42 through the AMPK/ULK/LC3B pathway in cells. Conclusions Our study showed that 40 Hz stimulating sound is involved in the inhibition of Aβ 42 secretion, p-Tau protein expression, and the promotion of phagocytosis and Aβ 42 autophagy in cells. We suggest that 40 Hz stimulating sound could be a potential intervention to attenuate AD progression in the future.