Molecular Differences and Similarities Between Alzheimer's Disease and the 5XFAD Transgenic Mouse Model of Amyloidosis.

Biochemistry Insights Pub Date : 2013-11-21 eCollection Date: 2013-01-01 DOI:10.4137/BCI.S13025
Chera L Maarouf, Tyler A Kokjohn, Charisse M Whiteside, MiMi P Macias, Walter M Kalback, Marwan N Sabbagh, Thomas G Beach, Robert Vassar, Alex E Roher
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引用次数: 47

Abstract

Transgenic (Tg) mouse models of Alzheimer's disease (AD) have been extensively used to study the pathophysiology of this dementia and to test the efficacy of drugs to treat AD. The 5XFAD Tg mouse, which contains two presenilin-1 and three amyloid precursor protein (APP) mutations, was designed to rapidly recapitulate a portion of the pathologic alterations present in human AD. APP and its proteolytic peptides, as well as apolipoprotein E and endogenous mouse tau, were investigated in the 5XFAD mice at 3 months, 6 months, and 9 months. AD and nondemented subjects were used as a frame of reference. APP, amyloid-beta (Aβ) peptides, APP C-terminal fragments (CT99, CT83, AICD), β-site APP-cleaving enzyme, and APLP1 substantially increased with age in the brains of 5XFAD mice. Endogenous mouse tau did not show age-related differences. The rapid synthesis of Aβ and its impact on neuronal loss and neuroinflammation make the 5XFAD mice a desirable paradigm to model AD.

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阿尔茨海默病与5XFAD转基因小鼠淀粉样变模型的分子异同
转基因(Tg)阿尔茨海默病(AD)小鼠模型已被广泛用于研究阿尔茨海默病(AD)的病理生理和测试药物治疗AD的疗效。5XFAD Tg小鼠含有两个早老素-1和三个淀粉样前体蛋白(APP)突变,旨在快速重现人类AD中存在的部分病理改变。在5XFAD小鼠3个月、6个月和9个月时研究APP及其蛋白水解肽,以及载脂蛋白E和内源性小鼠tau蛋白。AD和非痴呆被试作为参照系。5XFAD小鼠大脑中APP、β淀粉样蛋白(Aβ)肽、APP c端片段(CT99、CT83、AICD)、β位点APP切割酶和APLP1随着年龄的增长而显著增加。内源性小鼠tau蛋白没有表现出与年龄相关的差异。a β的快速合成及其对神经元损失和神经炎症的影响使5XFAD小鼠成为模拟AD的理想范例。
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Biochemistry Insights
Biochemistry Insights BIOCHEMISTRY & MOLECULAR BIOLOGY-
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