Molecular Differences and Similarities Between Alzheimer's Disease and the 5XFAD Transgenic Mouse Model of Amyloidosis.
Molecular Differences and Similarities Between Alzheimer's Disease and the 5XFAD Transgenic Mouse Model of Amyloidosis.
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DOI：
10.4137/bci.s13025
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发表时间：
2013
影响因子：
--
通讯作者：
Roher AE
中科院分区：
文献类型：
--
作者：
Maarouf CL;Kokjohn TA;Whiteside CM;Macias MP;Kalback WM;Sabbagh MN;Beach TG;Vassar R;Roher AE
阿尔茨海默病（AD）的转基因（Tg）小鼠模型已被广泛用于研究这种痴呆的病理生理学和测试治疗AD的药物的功效。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中存在的部分病理学改变。在3个月、6个月和9个月时，在5XFAD小鼠中研究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和非痴呆受试者被用作参照系。在5XFAD小鼠的脑中，APP、淀粉样β（Aβ）肽、APP C端片段（CT 99、CT 83、AICD）、β位点APP裂解酶和APLP 1随年龄增长而显著增加。内源性小鼠tau蛋白未显示出与年龄相关的差异。Aβ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AD模型的理想范例。
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.