Brain Aβ amyloidosis in APPsw mice induces accumulation of presenilin‐1 and tau
Brain Aβ amyloidosis in APPsw mice induces accumulation of presenilin‐1 and tau
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APPsw 小鼠脑部 Aβ 淀粉样变性诱导早老素-1 和 tau 蛋白积累
DOI：
10.1002/path.897
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发表时间：
2001
期刊：
影响因子：
--
通讯作者：
M. Shoji
中科院分区：
文献类型：
--
作者：
Y. Tomidokoro;Y. Harigaya;E. Matsubara;M. Ikeda;T. Kawarabayashi;T. Shirao;K. Ishiguro;K. Okamoto;S. Younkin;M. Shoji
过量产生突变型β淀粉样蛋白前体（βAPP）的APPsw转基因小鼠（Tg2576）表现出严重的脑部Aβ淀粉样变性和行为异常。为了阐明随后的异常情况，我们检查了神经元和突触的消失以及营养不良的神经突形成以及包括过度磷酸化tau蛋白在内的累积蛋白质。 Tg2576 表现出大量巨大的核心斑块和弥漫性斑块。在尼氏加刚果红双染切片中，与所有其他区域和非转基因同窝小鼠的相应区域相比，含有淀粉样蛋白核心的区域中的神经元数量显着减少（p<0.001）。淀粉样蛋白核心中也不存在突触前蛋白α-突触核蛋白和突触后蛋白drebrin。 βAPP 和早老素-1 在核心斑块内及其周围的营养不良的神经突中积累。在淀粉样蛋白核心的营养不良神经突中检测到 5 个独立位点磷酸化的 Tau 蛋白。因此，巨大的核心斑块取代了正常的脑组织，并与随后的病理特征相关，例如营养不良的神经突和过度磷酸化的tau蛋白的出现。这些发现表明大脑 Aβ 淀粉样变性在诱导导致阿尔茨海默病精神障碍的继发病理步骤中具有潜在作用。版权所有 © 2001 约翰·威利父子有限公司
APPsw transgenic mice (Tg2576) overproducing mutant amyloid β protein precursor (βAPP) show substantial brain Aβ amyloidosis and behavioural abnormalities. To clarify the subsequent abnormalities, the disappearance of neurons and synapses and dystrophic neurite formation with accumulated proteins including hyperphosphorylated tau were examined. Tg2576 demonstrated substantial giant core plaques and diffuse plaques. The number of neurons was significantly decreased in the areas containing the amyloid cores compared with all other areas and corresponding areas in non‐transgenic littermates in sections visualized by Nissl plus Congo red double staining (p<0.001). The presynaptic protein α‐synuclein and postsynaptic protein drebrin were also absent in the amyloid cores. βAPP and presenilin‐1 were accumulated in dystrophic neurites in and around the core plaques. Tau phosphorylated at five independent sites was detected in the dystrophic neurites in the amyloid cores. Thus, the giant core plaques replaced normal brain tissues and were associated with subsequent pathological features such as dystrophic neurites and the appearance of hyperphosphorylated tau. These findings suggest a potential role for brain Aβ amyloidosis in the induction of secondary pathological steps leading to mental disturbance in Alzheimer's disease. Copyright © 2001 John Wiley & Sons, Ltd.
DOI：
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发表时间：
1998
期刊：
The American journal of pathology
影响因子：
--
作者：
S. Frautschy;Fusheng Yang;Michael Irrizarry;B. Hyman;T. Saido;K. Hsiao;G. Cole
通讯作者：
S. Frautschy;Fusheng Yang;Michael Irrizarry;B. Hyman;T. Saido;K. Hsiao;G. Cole
影响因子：
6
作者：
Lippa, CF;Fujiwara, H;Trojanowski, JQ
通讯作者：
Trojanowski, JQ