| Summary: | 碩士 === 長榮大學 === 醫學研究所 === 96 === There are approximately 25 million Alzheimer’s disease (AD) patients in the world, and about 60％ of dementia patients were caused by AD in Taiwan. Senile plaques which are accumulated by amyloid beta (Aβ) and neurofibrillary tangles (NFTs) are the major hallmarks in the brain of AD patients. Some evidences have shown that inflammation and reactive oxygen species (ROS) increase in AD patients’ brain. But the pathogenesis of AD is unclear. Some risk factors of AD have been reported that include age, sex, genetics and chronic disease. The epidemiological studies have suggested that the levels of advanced glycation end products (AGEs) are enhanced in patients of diabetes mellitus (DM) and ageing procession. At the same time, the evidences indicated moderately increased risks to develop AD in diabetic patients. AGEs may play a role in the pathogenesis of AD. In this study, we proposed that amyloid precursor protein (APP) expression is regulated by AGEs in SH-SY5Y neuroblastoma cell line. Cells were treated with AGEs (0-5 mg/ml) and the expression of APP mRNA were detected, Aβ and ROS. Our data showed that APP mRNA and protein were up-regulated and cell viability was inhibited by AGEs. In the condition medium, the levels of Aβ were increased after AGEs treatment. Furthermore, the increased levels of ROS and cytotoxicity were dose- and time-dependent after cells treated with AGEs and Aβ. In this study, we suggested that AGEs may participate in AD formation through two different pathways. One involves APP gene and Aβ productions. Another, AGEs increased ROS and caused cell toxicity. This report indicated that AGEs maybe an important risk factor in
the pathogensis of AD.
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