Morphological characterization of thioflavin-S-positive amyloid plaques in transgenic Alzheimer mice and effect of passive Aβ immunotherapy on their clearance
Morphological characterization of thioflavin-S-positive amyloid plaques in transgenic Alzheimer mice and effect of passive Aβ immunotherapy on their clearance
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DOI：
10.1016/s0002-9440(10)63360-3
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发表时间：
2004-09-01
影响因子：
6
通讯作者：
Buttini, M
中科院分区：
文献类型：
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作者：
Bussière, T;Bard, F;Buttini, M
已经开发了模仿阿尔茨海默病（AD）病理学的某些特征（即淀粉样蛋白斑块和神经元缠结）的转基因小鼠，以更好地理解导致这些特征性脑病变形成的机制。最近，这些动物模型已被广泛用于研究旨在减少脑淀粉样蛋白负荷的紧急治疗。几项研究表明，靶向淀粉样蛋白肽（Abeta）的免疫疗法在清除淀粉样蛋白斑块或防止其形成方面是有效的，并且在减少这些动物中观察到的记忆/行为障碍方面是有效的。在AD中，不同类型的斑块可能具有不同的致病意义，PDAPP转基因小鼠中斑块病理学的进一步表征将增强对潜在治疗剂的评估。在本研究中，淀粉样蛋白斑块存在于PDAPP小鼠的大脑中的形态学分类建立了使用硫磺素-S染色。还研究了与淀粉样斑块相关的神经炎性营养不良。最后，研究了用抗Abeta抗体被动免疫对清除Thio-S阳性淀粉样蛋白斑块的功效。我们的研究结果表明，不同的形态类型的斑块差异清除取决于同种型的抗体。
Transgenic mice mimicking certain features of Alzheimer's disease (AD)-pathology, namely amyloid plaques and neurofibrillary tangles, have been developed in an effort to better understand the mechanism leading to the formation of these characteristic cerebral lesions. More recently, these animal models have been widely used to investigate emergent therapies aimed at the reduction of the cerebral amyloid load. Several studies have shown that immunotherapy targeting the amyloid peptide (Abeta) is efficacious at clearing the amyloid plaques or preventing their formation, and at reducing the memory/behavior impairment observed in these animals. in AD, different types of plaques likely have different pathogenic significance, and further characterization of plaque pathology in the PDAPP transgenic mice would enhance the evaluation of potential therapeutics. In the present study, a morphological classification of amyloid plaques present in the brains of PDAPP mice was established by using Thioflavin-S staining. Neuritic dystrophy associated with amyloid plaques was also investigated. Finally, the efficacy of passive immunization with anti-Abeta antibodies on the clearance of Thio-S positive amyloid plaques was studied. Our results show that distinct morphological types of plaques are differentially cleared depending upon the isotype of the antibody.