Type 1 diabetes exaggerates features of Alzheimer's disease in APP transgenic mice

被引：146

作者：

Jolivalt, Corinne G. ^{[1
]}

Hurford, Rosemarie ^{[1
]}

Lee, Corinne A. ^{[1
]}

Dumaop, Wilmar ^{[2
]}

Rockenstein, Edward ^{[2
]}

Masliah, Eliezer ^{[1
,2
]}

机构：

[1] Univ Calif San Diego, Dept Pathol, La Jolla, CA 92093 USA

[2] Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92093 USA

来源：

EXPERIMENTAL NEUROLOGY | 2010年 / 223卷 / 02期

关键词：

Alzheimer's disease; Diabetes; Neurodegenerative diseases; Insulin receptor; Glycogen synthase-kinase-3; Amyloid; Tau; GLYCOGEN-SYNTHASE KINASE-3; INSULIN-DEGRADING ENZYME; AMYLOID-BETA-PROTEIN; MOUSE MODEL; COGNITIVE IMPAIRMENT; SIGNALING PATHWAY; BRAIN INSULIN; TAU; RISK; DEMENTIA;

D O I：

10.1016/j.expneurol.2009.11.005

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

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 GSK3 beta activity. Concomitantly, tau phosphorylation and number of A beta 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. (C) 2009 Elsevier Inc. All rights reserved.

引用

页码：422 / 431

页数：10

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