The role of gonadotropins in regulating the production of Alzheimer's beta amyloid

目前，约有16万澳大利亚人患有痴呆症，其中50%-70%是阿尔茨海默病(AD)病例。AD的临床特征是记忆和人格改变，病理特征是淀粉样蛋白沉积。在疾病发病机制中特别重要的是一种名为β淀粉样蛋白的小分子，其过量生产被认为是阿尔茨海默病发展的核心。生殖激素水平的变化，特别是绝经期间雌激素水平或雄激素酶期间睾酮水平的降低，与AD发病风险的增加和β淀粉样蛋白水平的变化有关。此外，更年期和雄停经的特征还包括其他生殖激素的变化，如促性腺激素。高水平的促性腺激素也与AD风险的增加有关。因此，确定这些变化如何改变AD的风险是很重要的。这项研究考察了促性腺激素在细胞培养和AD动物模型中调节β淀粉样蛋白水平的作用。此外，这项研究将在动物模型中评估使用促性腺激素降低剂来降低β淀粉样蛋白水平。这项研究的结果将为生殖激素如何调节β淀粉样蛋白提供重要数据。对这些机制的进一步了解将为AD提供治疗或预防策略。

Currently, about 160,000 Australians suffer from dementia; of which 50-70% are Alzheimer's disease (AD) cases. AD is characterised clinically by memory and personality changes and pathologically by deposition of amyloid. Of particular importance in the disease pathogenesis, is a small molecule called beta amyloid, of which the overproduction is thought to be central to the development of AD. Changes in the levels of the reproductive hormones, particularly low levels of oestrogen during menopause or testosterone during andropuase, has been associated with the increased risk of developing AD and in altering the levels of beta amyloid. Furthermore, menopause and andropause are also characterised by changes in other reproductive hormones such as the gonadotropins. High levels of the gonadotropins have also been associated with the increased risk of developing AD. Therefore it is important to identify how these changes modify the risk of developing AD. This study examines the role of the gonadotropins in regulating beta amyloid levels in cell culture and in an animal model for AD. Furthermore, this study will assess, in the animal model, the use of gonadotropin lowering agents to reduce levels of beta amyloid. The results from this study will provide important data on how reproductive hormones regulate beta amyloid. Further insight into these mechanisms will provide therapeutic or preventative strategies for AD.