The Significance of Systemic Inflammation for Different Risk Factors in Developing Alzheimer's disease
Raymond Chuen-Chung Chang Laboratory of Neurodegenerative Diseases, School of Biomedical Sciences, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China
As we are gradually aware that development of Alzheimer's disease (AD) is multi-hit processes to build up neuropathology of senile plaques and neurofibrillary tangles, our research focus should be on different risk factors leading to AD. Aging markedly increases the prevalent of AD. Our life time exposure to different risk factors and personal life style contribute to the multi-hits processes to develop neuropathology and cognitive impairment. Epidemiological studies have informed us different risk factors such as depression, infection, environmental pollutants, and even post-operative cognitive dysfunctions. For years, our research team has been using different experimental disease models for the risk factors and finding the convergent key factors leading to start the program of neurodegeneration. Our current hypothesis is that immune responses in our body (systemic inflammation) can trigger neuroimmune responses (neuroinflammation), which then lead to the accumulation of neuropathology and then cognitive impairment. We have used several experimental models to prove our hypothesis. First, by loading live bacteria (E. Coli) into subcutaneous will induce cytokines production from the liver and the brain. This will induce sickness behaviour, a pre-condition of depression and cognitive dysfunction. Second, by using laparotomy as experimental model of post-operative cognitive dysfunction, we demonstrate similar pattern of events. We can continue to further demonstrate in the third model of chronic kidney disease and fourth model of periodontitis. As long as we can attenuate systemic inflammation by preventive methods, we can inhibit neuroinflammation and cognitive dysfunction. Our study not only reveal a key factor in neurodegeneration but also reshape future clinical practice for treatment of different diseases to preserve cognitive functions and to protect the brain.
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