Type 1 diabetes exaggerates features of Alzheimer's disease in APP transgenic mice.
Type 1 diabetes exaggerates features of Alzheimer's disease in APP transgenic mice.
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DOI：
10.1016/j.expneurol.2009.11.005
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发表时间：
2010-06
影响因子：
5.3
通讯作者：
Masliah, Eliezer
中科院分区：
文献类型：
--
作者：
Jolivalt, Corinne G.;Hurford, Rosemarie;Lee, Corinne A.;Dumaop, Wilmar;Rockenstein, Edward;Masliah, Eliezer
关键词：
许多研究表明，阿尔茨海默病（AD）和糖尿病之间存在关联：AD患者表现为胰岛素功能受损，而认知缺陷和患AD的风险增加发生在糖尿病患者身上。风险增加的原因尚不清楚。最近对胰岛素信号通路紊乱的研究揭示了AD与1型糖尿病之间联系的新视角，特别是糖原合成酶-激酶-3 （GSK3）。因此，我们对胰岛素缺乏性糖尿病和AD合并的小鼠模型进行了表征，发现糖尿病放大了APP转基因小鼠的大脑缺陷。APP过表达和糖尿病合并的小鼠表现出胰岛素受体活性降低和GSK3β活性升高。与此同时，在糖尿病- app转基因小鼠的大脑中，AD的两个病理标志tau磷酸化和β斑块数量增加。我们的研究结果表明，AD的病理特征在同时患有胰岛素缺乏性糖尿病的APP转基因小鼠的大脑中被夸大，并强调了AD和糖尿病共同的脑功能障碍的可能机制。
A number of studies suggest an association between Alzheimer's disease (AD) and diabetes: AD patients show impaired insulin function, whereas cognitive deficits and increased risk of developing AD occur in diabetic patients. The reasons for the increased risk are not known. Recent studies of disturbances in the insulin-signaling pathway have revealed new perspectives on the links between AD and Type 1 diabetes with a particular focus on glycogen synthase-kinase-3 (GSK3). We have therefore characterized a mouse model of combined insulin-deficient diabetes and AD and find that diabetes exaggerated defects in the brain of APP transgenic mice. Mice with combined APP overexpression and diabetes showed a decreased insulin receptor activity and an increased GSK3β activity. Concomitantly, tau phosphorylation and number of Aβ plaques, the two pathologic hallmarks of AD, were increased in the brain of diabetic-APP transgenic mice. Our results indicate that the pathologic features of AD are exaggerated in the brain of APP transgenic mice that have concurrent insulin-deficient diabetes, and underscore a possible mechanism of brain dysfunction common to AD and diabetes.
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DOI：
10.1083/jcb.200301115
发表时间：
2003-10-13
期刊：
The Journal of cell biology
影响因子：
--
作者：
Lee MS;Kao SC;Lemere CA;Xia W;Tseng HC;Zhou Y;Neve R;Ahlijanian MK;Tsai LH
通讯作者：
Tsai LH
影响因子：
4.2
作者：
Burdo, Joseph R.;Chen, Qi;Schubert, David
通讯作者：
Schubert, David
影响因子：
4.7
作者：
Gruenblatt, Edna;Salkovic-Petrisic, Melita;Hoyer, Siegfried
通讯作者：
Hoyer, Siegfried
DOI：
10.1037/h0077579
发表时间：
1979-01-01
期刊：
JOURNAL OF COMPARATIVE AND PHYSIOLOGICAL PSYCHOLOGY
影响因子：
--
作者：
BARNES, CA
通讯作者：
BARNES, CA
影响因子：
1.7
作者：
Brownlees, J;Irving, NG;Miller, CCJ
通讯作者：
Miller, CCJ