The pathological interaction between diabetes and presymptomatic Alzheimer's disease
The pathological interaction between diabetes and presymptomatic Alzheimer's disease
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DOI：
10.1016/j.neurobiolaging.2008.02.010
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发表时间：
2009-12-01
影响因子：
4.2
通讯作者：
Schubert, David
中科院分区：
文献类型：
--
作者：
Burdo, Joseph R.;Chen, Qi;Schubert, David
由于糖尿病是阿尔茨海默病（AD）的危险因素，我们询问在培养的脑微血管内皮细胞和症状前AD转基因小鼠中，高糖和升高的β淀粉样肽（AD）之间是否存在功能性相互作用。当培养的脑微血管内皮细胞暴露于高葡萄糖和低水平的AD时，存在协同相互作用，导致晚期糖基化产物（AGE）和反应性氧物种（ROS）的积累增加。当表达突变的人淀粉样前体蛋白和早老素的症状前小鼠患糖尿病时，它们的认知功能相对于对照小鼠有所下降。与认知缺陷相关的是脑微血管AGE和iNOS表达的增加。以及突触棘蛋白的丢失。在任何组的脑内均未观察到淀粉样蛋白斑块或缠结。这些数据表明，糖尿病在转基因动物中引起AD的一些指数的协同增强，所述转基因动物是该疾病的典型特征的先兆（C）2008 Elsevier Inc. All rights reserved.
Since diabetes is a risk factor for Alzheimer's disease (AD), we asked if there is a functional interaction between high glucose and elevated beta amyloid peptide (AD) in cultured brain microvascular endothelial cells and presymptomatic AD transgenic mice. When cultured brain microvascular endothelial cells are exposed to both high glucose and low levels of AD, there is a synergistic interaction to cause an increased accumulation of advanced glycation products (AGE) and reacuve oxygen species (ROS). When presymptomatic mice expressing mutant human amyloid precursor protein and presenilin are made diabetic, they have a decrease in cognitive function relative to control mice. Associated with the cognitive deficit are increases in brain microvascular AGE and iNOS expression. and the loss of the synaptic spine protein drebrin. No amyloid plaques or tangles are observed within the brains of any group. These data show that diabetes causes a synergistic potentiation of some indices of AD in transgenic animals that are presymptomatic for the classical features of the disease (C) 2008 Elsevier Inc. All rights reserved.