A transgenic rat model of Alzheimer's disease with extracellular Aβ deposition

被引：61

作者：

Flood, Dorothy G. ^{[1
]}

Lin, Yin-Guo ^{[1
]}

Lang, Diane M. ^{[1
]}

Trusko, Stephen P. ^{[1
]}

Hirsch, James D. ^{[1
]}

Savage, Mary J. ^{[1
]}

Scott, Richard W. ^{[1
]}

Howland, David S. ^{[1
]}

机构：

[1] Cephalon Inc, Discovery Res, Dept CNS Biol, W Chester, PA 19380 USA

来源：

NEUROBIOLOGY OF AGING | 2009年 / 30卷 / 07期

关键词：

Amyloid; Presenilin; Alzheimer's disease; A beta deposition; Rat; Animal model; Transgenic; Reactive gliosis; Phosphorylated tau; AMYLOID PRECURSOR PROTEIN; CEREBRAL-CORTEX; MOUSE MODELS; B-CHAIN; PRESENILIN-1; NEURONS; MICE; HIPPOCAMPUS; MUTANT; BRAIN;

D O I：

10.1016/j.neurobiolaging.2007.10.006

中图分类号：

R592 [老年病学]; C [社会科学总论];

学科分类号：

03 ; 0303 ; 100203 ;

摘要：

Many transgenic mouse models of Alzheimer's disease (AD) that deposit amyloid (A beta) have been produced, but development of an A beta-depositing rat model has not been successful. Here, we describe a rat model with extracellular fibrillar A beta deposition. Two lines of Sprague Dawley rats with transgenes expressing human amyloid precursor protein (APP) with the familial AD (FAD) mutations K670N/M671L and K670N/M671L/V717I were crossed. A beta production in the double homozygous rats was sufficient for deposition by 17-18 months of age. The age of onset of A beta deposition was reduced by crossing in a third rat line carrying a human presenitin-1 (PS-1) transgene with the FAD M146V mutation. The triple homozygous line had an onset of A beta deposition by 7 months of age. Deposits appeared similar to those observed in the mouse models and displayed surrounding glial and phosphorylated tau reactivity. A beta levels measured by ELISA were comparable to those reported in mouse models, suggesting that substantially greater amounts of soluble A beta are not required in the rat to generate A beta deposition. (C) 2007 Elsevier Inc. All rights reserved.

引用

页码：1078 / 1090

页数：13

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