Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by the deposition of amyloid-β (Aβ), neurofibrillary tangles, neuroinflammation, and neurodegeneration in the brain. In recent years, considering the unsatisfied benefits of pharmacological therapies, non-pharmacological therapy has become a research hotspot for AD intervention. Terahertz (THz) waves with a range between microwave and infrared regions in the electromagnetic spectrum and high permeability to a wide range of materials have great potential in the bioengineering field. However, its biological impacts on the central nervous system, under either physiological or pathological conditions, are poorly investigated. In this study, we first measured the 0.14 THz waves penetration across the skull of a C57BL/6 mouse and found the percentage of THz penetration to be ~70%, guaranteeing that THz waves can reach the relevant brain regions. We then exposed the APP^SWE/PS1^DE9 mouse model of AD to repeated low-frequency THz waves on the head. We demonstrated that THz waves treatment significantly improved the cognitive impairment and alleviated AD neuropathology including Aβ deposition and tau hyperphosphorylation in the AD mice. Moreover, THz waves treatment effectively attenuated mitochondrial impairment, neuroinflammation, and neuronal loss in the AD mouse brain. Our findings reveal previously unappreciated beneficial effects of THz waves treatment in AD and suggest that THz waves may have the potential to be used as a novel therapeutic intervention for this devastating disease.

阿尔茨海默病 (AD) 是一种进行性神经退行性疾病，其特征是大脑中淀粉样蛋白 (Aβ) 沉积、神经原纤维缠结、神经炎症和神经变性。近年来，鉴于药物治疗的疗效未得到满足，非药物治疗已成为AD干预的研究热点。太赫兹（THz）波的范围介于电磁波谱中的微波和红外区域之间，并且对多种材料具有高渗透性，在生物工程领域具有巨大的潜力。然而，其在生理或病理条件下对中枢神经系统的生物学影响却很少被研究。在本研究中，我们首先测量了0.14太赫兹波穿过C57BL/6小鼠头骨的穿透率，发现太赫兹波穿透率约为70%，保证了太赫兹波可以到达相关的大脑区域。然后，我们将 AD 的 APP ^SWE /PS1 ^DE9小鼠模型暴露在头部重复的低频太赫兹波中。我们证明，太赫兹波治疗可显着改善 AD 小鼠的认知障碍并减轻 AD 神经病理学，包括 Aβ 沉积和 tau 蛋白过度磷酸化。此外，太赫兹波治疗有效减轻了 AD 小鼠大脑中的线粒体损伤、神经炎症和神经元损失。我们的研究结果揭示了太赫兹波治疗 AD 之前未被认识到的有益效果，并表明太赫兹波可能有潜力用作这种破坏性疾病的新型治疗干预措施。