Targeting amyloid-β peptide (Aβ) oligomers by passive immunization with a conformation-selective monoclonal antibody improves learning and memory in Aβ precursor protein (APP) transgenic mice
Targeting amyloid-β peptide (Aβ) oligomers by passive immunization with a conformation-selective monoclonal antibody improves learning and memory in Aβ precursor protein (APP) transgenic mice
复制标题
DOI：
10.1074/jbc.m511018200
复制
发表时间：
2006-02-17
影响因子：
4.8
通讯作者：
Lee, VMY
中科院分区：
文献类型：
--
作者：
Lee, EB;Leng, LZ;Lee, VMY
阿尔茨海默病淀粉样变性小鼠模型的被动免疫降低淀粉样β肽（A β）水平并改善认知功能。为了明确A β寡聚体在学习和记忆中的作用，我们产生了一种新型单克隆抗体NAB 61，其优先识别存在于二聚体、小寡聚体和高阶A β结构中的构象表位，但不识别全长淀粉样蛋白-β前体蛋白或C-末端淀粉样蛋白-β前体蛋白片段。NAB 61还识别脑A β沉积物的子集，优选成熟老年斑和淀粉样血管病。使用NAB 61作为免疫疗法，我们发现用NAB 61治疗的老年Tg 2576转基因小鼠相对于对照小鼠在空间学习和记忆方面显示出显著改善。这些数据表明A β寡聚体是阿尔茨海默病认知功能下降的病理底物。
Passive immunization of murine models of Alzheimer disease amyloidosis reduces amyloid-beta peptide (A beta) levels and improves cognitive function. To specifically address the role of A beta oligomers in learning and memory, we generated a novel monoclonal antibody, NAB61, that preferentially recognizes a conformational epitope present in dimeric, small oligomeric, and higher order A beta structures but not full-length amyloid-beta precursor protein or C-terminal amyloid-beta precursor protein fragments. NAB61 also recognized a subset of brain A beta deposits, preferentially mature senile plaques, and amyloid angiopathy. Using NAB61 as immunotherapy, we showed that aged Tg2576 transgenic mice treated with NAB61 displayed significant improvements in spatial learning and memory relative to control mice. These data implicated A beta oligomers as a pathologic substrate for cognitive decline in Alzheimer disease.