Amyloid β protein dimer-containing human CSF disrupts synaptic plasticity:: Prevention by systemic passive immunization
Amyloid β protein dimer-containing human CSF disrupts synaptic plasticity:: Prevention by systemic passive immunization
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DOI：
10.1523/jneurosci.5161-07.2008
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发表时间：
2008-04-16
影响因子：
5.3
通讯作者：
Rowan, Michael J.
中科院分区：
文献类型：
--
作者：
Klyubin, Igor;Betts, Vicki;Rowan, Michael J.
目前治疗阿尔茨海默病的免疫疗法的发展是基于这样的假设，即人类来源的淀粉样β蛋白(Aβ)可以以类似于动物细胞来源或合成的Aβ的方式被靶向。由于Aβ的结构取决于其来源和辅因子的存在，因此确定人类来源的寡聚Aβ物种是否会损害大脑功能，如果是的话，是否可以用抗体阻止其破坏作用，这是非常有意义的。我们报道，含有Aβ二聚体的未经处理的体外人类脑脊液在体内迅速抑制海马区的长时程增强，急性全身注射抗Aβ单抗可以防止这种突触可塑性的破坏。从人脑脊液中分离出的β单体不影响长时程增强。这些结果有力地支持了在早期阿尔茨海默病中针对可溶性Aβ寡聚体的被动免疫策略。
The current development of immunotherapy for Alzheimer's disease is based on the assumption that human-derived amyloid beta protein ( A beta) can be targeted in a similar manner to animal cell-derived or synthetic A beta. Because the structure of A beta depends on its source and the presence of cofactors, it is of great interest to determine whether human-derived oligomeric A beta species impair brain function and, if so, whether or not their disruptive effects can be prevented using antibodies. We report that untreated ex vivo human CSF that contains A beta dimers rapidly inhibits hippocampal long-term potentiation in vivo and that acute systemic infusion of an anti-A beta monoclonal antibody can prevent this disruption of synaptic plasticity. A beta monomer isolated from human CSF did not affect long-term potentiation. These results strongly support a strategy of passive immunization against soluble A beta oligomers in early Alzheimer's disease.