The effect of noise induced hearing loss on Alzheimer's disease development and progression

点击翻译按钮获取中文摘要

Summary Alzheimer's disease (AD) is a common neurodegenerative disease characterized by a progressive loss of memory and cognitive decline. Over the last decade, the prevalence of AD and AD-related dementia (ADRD) has been rapidly growing. It is predicted that there will be 150 million AD patients by the year 2050, tripling the number in 2018. This will cause severe economic and social burdens. It has been estimated that speeding up the onset of dementia by even one year would increase the worldwide prevalence of dementia by 10%. However, currently, little is known about causes or mechanisms for this rapid increase in AD population. Many factors, particularly environmental factors, have been proposed as potential contributors to this rapid increase. Noise is a common high-risk environmental factor for human health and also a common deafness factor. Noise can induce hearing loss; hearing loss can induce and accelerate cognitive decline. In particular, recent studies demonstrate that noise can induce hidden hearing loss (HHL), which is caused by noise-induced inner hair cell synapse degeneration leading to difficulty of speech understanding in communication and therefore eventually social isolation. Currently, our world is becoming more and more noisy due to traffic, TV, and wide use of personal audio and video devices. We hypothesize that noise is a high-risk factor for AD development and may play an important role in AD population growing. To test this novel hypothesis, we will investigate whether noise can accelerate AD development and progression in AD mice (Aim 1). We will also investigate whether AD can impair the cochlear efferent system, which plays a critical role in the protection of hearing from noise, to increase susceptibility to noise and in turn to accelerate AD development and progression (Aim 2). In Aim 3, we will further investigate whether deficiency of ATP-purinergic function can accelerate AD development and progression, since our previous study found that deficiency of ATP-purinergic signaling function could induce hearing loss and increase susceptibility to noise. ATP-purinergic signaling also plays an important role in neuroinflammation, which is a consequence of noise exposure and plays a critical role in AD development and progression. Therefore, ATP-purinergic receptors have been considered an excellent potential target as well for AD prevention and treatment after anti-amyloid clinical trials have failed. These proposed studies will help to identify high-risk factors or contributors to the rapidly growth of the AD population and elucidate underlying mechanisms, thereby laying the foundation for development of new preventive and therapeutic interventions for AD and ADRD. Particularly, recent studies reported that visual and auditory stimulations with gamma oscillation cycles could reduce Aȕ expression in the brain and improve memory in AD mice, further indicating that the auditory system has a critical role in AD development and progression.