Apolipoprotein D modulates amyloid pathology in APP/PS1 Alzheimer's disease mice
Apolipoprotein D modulates amyloid pathology in APP/PS1 Alzheimer's disease mice
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DOI：
10.1016/j.neurobiolaging.2015.02.010
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发表时间：
2015-05-01
影响因子：
4.2
通讯作者：
Garner, Brett
中科院分区：
文献类型：
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作者：
Li, Hongyun;Ruberu, Kalani;Garner, Brett
载脂蛋白D（apoD）在脑中表达，并且在阿尔茨海默病（AD）中受影响的脑区域中水平增加。apoD在调节AD病理学中可能发挥的作用尚未得到解决。在这里，我们将apoD基因敲除小鼠和Thy-1人apoD转基因小鼠与APP-PS1淀粉样蛋白生成性AD小鼠杂交。apoD的缺失导致海马淀粉样斑块负荷增加近2倍，通过免疫组化染色进行评估。相反，神经元apoD的转基因表达减少海马斑块负荷约35%。后一项发现与淀粉样β 1-40肽水平降低60%和不溶性淀粉样β 1-42肽降低34%相关。β位点淀粉样前体蛋白裂解酶-1（BACE 1）水平和淀粉样前体蛋白和神经调节蛋白-1的蛋白水解产物的评估指向BACE 1活性改变与apoD水平改变的可能关联。总之，目前的研究提供了明确的证据，apoD调节淀粉样蛋白斑块病理在小鼠模型的AD。(C)2015 Elsevier Inc. All rights reserved.
Apolipoprotein D (apoD) is expressed in the brain and levels are increased in affected brain regions in Alzheimer's disease (AD). The role that apoD may play in regulating AD pathology has not been addressed. Here, we crossed both apoD-null mice and Thy-1 human apoD transgenic mice with APP-PS1 amyloidogenic AD mice. Loss of apoD resulted in a nearly 2-fold increase in hippocampal amyloid plaque load, as assessed by immunohistochemical staining. Conversely, transgenic expression of neuronal apoD reduced hippocampal plaque load by approximately 35%. This latter finding was associated with a 60% decrease in amyloid beta 1-40 peptide levels, and a 34% decrease in insoluble amyloid beta 1-42 peptide. Assessment of beta-site amyloid precursor protein cleaving enzyme-1 (BACE1) levels and proteolytic products of amyloid precursor protein and neuregulin-1 point toward a possible association of altered BACE1 activity in association with altered apoD levels. In conclusion, the current studies provide clear evidence that apoD regulates amyloid plaque pathology in a mouse model of AD. (C) 2015 Elsevier Inc. All rights reserved.