40 Hz acoustic stimulation decreases amyloid beta and modulates brain rhythms in a mouse model of Alzheimers disease

IntroductionThe accumulation of amyloid-beta (A{beta}) is one of the neuropathologic hallmarks of Alzheimers disease (AD) and abnormal gamma band oscillations and brain connectivity have been observed. Recently, a therapeutic potential of gamma entrainment of the brain was reported by Iaccarino et al. However, the affected areas were limited to hippocampus and visual cortex. Therefore, we sought to test the effects of acoustic stimulation in a mouse model of AD.\n\nMethodsFreely moving 6-month-old 5XFAD mice with electroencephalogram (EEG) electrodes were treated with daily two-hour acoustic stimulation at 40Hz for 2 weeks. A{beta} and microglia were evaluated by immunohistochemistry and ELISA. Evoked and spontaneous gamma power were analyzed by wavelet analysis. Coherence, phase locking value (PLV), and cross-frequency coupling were analyzed.\n\nResultsThe number of A{beta} plaques decreased in the pre-and infralimbic (PIL) and hippocampus regions and soluble A{beta}-40 and A{beta}-42 peptides in PIL in the acoustic stimulation group. We also found that the number of microglia increased in PIL and hippocampus. In EEG analysis, evoked gamma power was decreased and spontaneous gamma power was increased. Gamma coherence and phase locking value did not show significant changes. Cross-frequency coupling was shifted from gamma-delta to gamma-theta rhythm.\n\nConclusionIn summary, we found that acoustic stimulation at 40Hz can reduce A{beta} in the brain and restore the gamma band oscillations and the frontoparietal connectivity. Our data suggest that acoustic stimulation might alter the natural deterioration processes of AD and have a therapeutic potential in AD.