阿尔茨海默病（AD）是导致老年人痴呆的最常见疾病，Ⅱ型糖尿病明显了增加AD的发生危险，但是，其机制不清楚。近年来，在AD患者中发现血浆IAPP水平升高与认知功能障碍的发生密切相关。在AD动物模型，证明脑内淀粉样斑块中存在IAPP。体外实验证明星形胶质细胞中存在IAPP。IAPP水平升高导致认知功能障碍，是外周来源IAPP还是星形胶质细胞IAPP起主要作用，尚存争议。伴糖尿病的AD中，IAPP与脑内Aβ沉积以及与淀粉样斑块的关系，目前尚无相关文献报道。我们设想IAPP促进脑内Aβ沉积可能是伴糖尿病AD发生发展的关键分子机制。本实验通过APP/IAPP转基因小鼠动物模型，探讨IAPP与Aβ沉积、淀粉样斑块形成及认知功能变化的关系。探讨外周IAPP与脑内星形胶质细胞产生的IAPP和AD病理特征形成之间的关系；进一步探讨IAPP类似物的干预作用为伴糖尿病AD的药物治疗提供实验依据。

Alzheimer’s disease is the most common cause of dementia in the elder, type II diabetes significantly increased the risk of AD incidence. However, the pathogenesis between these two common diseases is unclear. In recent years, plasma IAPP levels have been significantly elevated in patients with diabetes and AD. In AD patients, IAPP levels were found to be associated with cognitive dysfunction. It is speculated that peripheral IAPP can enter the brain through BBB. IAPP was present in astrocytes in vitro experiments. By immunohistochemical method, IAPP was present in amyloid plaques. However, whether IAPP promotes Aβ deposition in brain, and IAPP from peripheral plasma or astrocyte secretion play a major role is not clear. The relationship of IAPP with Aβ deposition or amyloid plaque in AD with diabetes has not been reported at home and abroad. We hypothesized that IAPP plays a key role for the development of AD with diabetes. In this study, we studied the relationship between IAPP and Aβ deposition, amyloid plaque formation and cognitive function by animal model of AD with diabetes mice. We also explored the intervention effect of IAPP analogues in order to provide experimental basis for the treatment of diabetes mellitus with AD.