Dodart Jean-Cosme, Bales Kelly R, Gannon Kimberley S, Greene Stephen J, DeMattos Ronald B, Mathis Chantal, DeLong Cynthia A, Wu Su, Wu Xin, Holtzman David M, Paul Steven M
Neuroscience Discovery Research, Lilly Research Laboratories, Lilly Corporate Center, Indianapolis, Indiana 46285, USA.
Nat Neurosci. 2002 May;5(5):452-7. doi: 10.1038/nn842.
We have previously shown that chronic treatment with the monoclonal antibody m266, which is specific for amyloid beta-peptide (Abeta), increases plasma concentrations of Abeta and reduces Abeta burden in the PDAPP transgenic mouse model of Alzheimer's disease (AD). We now report that administration of m266 to PDAPP mice can rapidly reverse memory deficits in both an object recognition task and a holeboard learning and memory task, but without altering brain Abeta burden. We also found that an Abeta/antibody complex was present in both the plasma and the cerebrospinal fluid of m266-treated mice. Our data indicate that passive immunization with this anti-Abeta monoclonal antibody can very rapidly reverse memory impairment in certain learning and memory tasks in the PDAPP mouse model of AD, owing perhaps to enhanced peripheral clearance and (or) sequestration of a soluble brain Abeta species.
我们之前已经表明，用针对淀粉样β肽（Aβ）的单克隆抗体m266进行长期治疗，可提高Aβ的血浆浓度，并减轻阿尔茨海默病（AD）的PDAPP转基因小鼠模型中的Aβ负荷。我们现在报告，给PDAPP小鼠施用m266可在物体识别任务和穿孔板学习记忆任务中迅速逆转记忆缺陷，但不会改变脑内Aβ负荷。我们还发现，在接受m266治疗的小鼠的血浆和脑脊液中均存在Aβ/抗体复合物。我们的数据表明，用这种抗Aβ单克隆抗体进行被动免疫可在AD的PDAPP小鼠模型的某些学习和记忆任务中非常迅速地逆转记忆损伤，这可能是由于增强了外周清除和（或）隔离了可溶性脑Aβ物种。
