Reduced effectiveness of Aβ1-42 immunization in APP transgenic mice with significant amyloid deposition
Reduced effectiveness of Aβ1-42 immunization in APP transgenic mice with significant amyloid deposition
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DOI：
10.1016/s0197-4580(01)00245-7
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发表时间：
2001-09-01
影响因子：
4.2
通讯作者：
Golde, TE
中科院分区：
文献类型：
--
作者：
Das, P;Murphy, MP;Golde, TE
已证明A β 1 -42疫苗接种可减少阿尔茨海默病（AD）转基因模型中的淀粉样蛋白负荷。我们通过免疫一组具有最小A β沉积的小鼠、一组具有中等A β沉积的小鼠和一组具有显著A β沉积的小鼠，进一步测试了A β 1 -42免疫在Tg 2576 AD小鼠模型中的功效。免疫对A β沉积的影响采用生物化学和免疫组织化学方法进行了研究。在显著淀粉样蛋白沉积之前免疫的Tg 2576小鼠中，A β 1 -42免疫非常有效。生化提取的A β 40和A β 42水平显著降低，免疫组化斑块负荷也降低。用适量预先存在的A β沉积物免疫小鼠，选择性地减少了A β 42，而不改变A β 40，尽管斑块负荷减少。相反，在具有显著预先存在的A β负荷的Tg 2576小鼠中，A β 1 -42免疫仅最低限度地降低A β 42水平，而未观察到A β 40水平或斑块负荷的改变。这些结果表明，在Tg 2576小鼠中，A β 1 -42免疫在预防额外的A β积累方面更有效，并且不会导致预先存在的A β沉积物的显著清除。(C)2001 Elsevier Science Inc. All rights reserved.
Vaccinations with A beta1-42 have been shown to reduce amyloid burden in transgenic models of Alzheimer's disease (AD). We have further tested the efficacy of A beta1-42 immunization in the Tg2576 mouse model of AD by immunizing one group of mice with minimal A beta deposition, one group of mice with modest A beta deposition, and one group with significant A beta deposition. The effects of immunization on A beta deposition were examined using biochemical and immunohistochemical methods. In Tg2576 mice immunized prior to significant amyloid deposition, A beta1-42 immunization was highly effective. Biochemically extracted A beta 40 and A beta 42 levels were significantly reduced and immunohistochemical plaque load was also reduced. Immunization of mice with modest amounts of pre-existing A beta deposits selectively reduced A beta 42 without altering A beta 40, although plaque load was reduced. In contrast, in Tg2576 mice with significant pre-existing A beta loads, A beta1-42 immunization only minimally decreased A beta 42 levels, whereas no alteration in A beta 40 levels or in plaque load was observed. These results indicate that in Tg2576 mice, A beta1-42 immunization is more effective at preventing additional A beta accumulation and does not result in significant clearance of pre-existing A beta deposits. (C) 2001 Elsevier Science Inc. All rights reserved.