Terahertz Irradiation Improves Cognitive Impairments and Attenuates Alzheimer’s Neuropathology in the APPSWE/PS1DE9 Mouse: A Novel Therapeutic Intervention for Alzheimer's Dis

 Jun Zhang1  · Yixin Chen1  · Yarui Zhao2  · Panpan Wang1  · Hongbin Ding2  · Cong Liu3  · Junhong Lyu4  · Weidong Le1,5
1 Liaoning Provincial Key Laboratory for Research on the Pathogenic Mechanisms of Neurological Diseases, the First Afliated Hospital, Dalian Medical University, Dalian 116011, China 
2 School of Physics, Dalian University of Technology, Dalian 116024, China 
3 Interdisciplinary Research Center on Biology and Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 201210, China 
4 Advanced Research Institute, Chinese Academy of Sciences, Shanghai 201203, China 
5 Department of Neurology and Institute of Neurology, Sichuan Academy of Medical Sciences-Sichuan Provincial Hospital, Medical School, University of Electronic Science and Technology of China, Chengdu 610072, China

Abstract
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 APPSWE/PS1DE9 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.

Keywords
Alzheimer’s disease; Cognitive impairment; Senile plaque; Tau protein; Terahertz