Research Progress on the Etiology and Pathogenesis of Alzheimer's Disease from the Perspective of Chronic Stress

Abstract

Due to its extremely complex pathogenesis, no effective drugs to prevent, delay progression, or cure Alzheimer's disease (AD) exist at present. The main pathological features of AD are senile plaques composed of β-amyloid, neurofibrillary tangles formed by hyperphosphorylation of the tau protein, and degeneration or loss of neurons in the brain. Many risk factors associated with the onset of AD, including gene mutations, aging, traumatic brain injury, endocrine and cardiovascular diseases, education level, and obesity. Growing evidence points to chronic stress as one of the major risk factors for AD, as it can promote the onset and development of AD-related pathologies via a mechanism that is not well known. The use of murine stress models, including restraint, social isolation, noise, and unpredictable stress, has contributed to improving our understanding of the relationship between chronic stress and AD. This review summarizes the evidence derived from murine models on the pathological features associated with AD and the related molecular mechanisms induced by chronic stress. These results not only provide a retrospective interpretation for understanding the pathogenesis of AD, but also provide a window of opportunity for more effective preventive and identifying therapeutic strategies for stress-induced AD.