Sima Anders A F, Li Zhen-Guo
Departments of Pathology, Wayne State University, School of Medicine, Detroit, MI 48201, USA.
Rev Diabet Stud. 2006 Winter;3(4):161-8. doi: 10.1900/RDS.2006.3.161. Epub 2007 Feb 10.
It has been known for some time that diabetes may be associated with impaired cognitive function. During the last decade, epidemiological data have emerged suggesting a linkage between diabetes, particularly type 2 diabetes, and Alzheimer's disease (AD). There is evidence to suggest that impaired activities of neurotrophic factors such as insulin, IGF-1 and NGF, which occur in both diabetes and AD, may provide a mechanistic link between the two disorders. An additional probable factor that has been less evaluated to date is hypercholesterolemia, a common accompaniment to type 2 diabetes. Increased cholesterol availability is believed to play a crucial role in the abnormal metabolism of amyloid precursor protein leading to accumulation of amyloid-beta. Impaired insulin signaling in particular appears to be involved in hyperphosphorylation of the tau protein, which constitutes neurofibrillary tangles in AD. The linkage between abnormal amyloid metabolism and phosphor-tau is likely to be provided by the activation of caspases both by increased amyloid-beta and by impaired insulin signaling. Although the details of many of these components still await evaluation, it appears clear that commonalities exist in the underlying pathogenesis of diabetes and Alzheimer's disease. In this review we provide a brief update on linkages between these two diverse but common disorders.
一段时间以来，人们已经知道糖尿病可能与认知功能受损有关。在过去十年中，流行病学数据显示糖尿病，尤其是2型糖尿病，与阿尔茨海默病（AD）之间存在联系。有证据表明，糖尿病和AD中均出现的胰岛素、胰岛素样生长因子-1（IGF-1）和神经生长因子（NGF）等神经营养因子活性受损，可能为这两种疾病之间提供了一种机制上的联系。迄今为止较少评估的另一个可能因素是高胆固醇血症，它是2型糖尿病的常见伴随症状。胆固醇可用性增加被认为在淀粉样前体蛋白的异常代谢中起关键作用，导致β-淀粉样蛋白的积累。特别是胰岛素信号受损似乎与tau蛋白的过度磷酸化有关，tau蛋白在AD中构成神经原纤维缠结。淀粉样蛋白代谢异常与磷酸化tau之间的联系可能是由β-淀粉样蛋白增加和胰岛素信号受损激活半胱天冬酶所导致的。尽管这些成分中的许多细节仍有待评估，但糖尿病和阿尔茨海默病的潜在发病机制显然存在共性。在本综述中，我们简要介绍了这两种不同但常见疾病之间的联系。
