Aβ peptide immunization reduces behavioural impairment and plaques in a model of Alzheimer's disease
Aβ peptide immunization reduces behavioural impairment and plaques in a model of Alzheimer's disease
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DOI：
10.1038/35050110
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发表时间：
2000-12-21
期刊：
影响因子：
64.8
通讯作者：
Westaway, D
中科院分区：
文献类型：
--
作者：
Janus, C;Pearson, J;Westaway, D
许多证据表明，淀粉样β肽（A β）（β-淀粉样前体蛋白（β APP）的蛋白水解衍生物）的异常加工和细胞外沉积是阿尔茨海默病发病机制的核心（综述见参考文献1）。在阿尔茨海默病的PDAPP转基因小鼠模型中，用Ab免疫导致脑淀粉样蛋白负荷的显著降低（2，3）。A β免疫也减少阿尔茨海默病小鼠模型中的认知功能障碍的证据将支持异常A β加工对阿尔茨海默病的发病机制至关重要的假设，并将鼓励针对“淀粉样蛋白级联”的其他策略的发展。在这里，我们表明，A β免疫减少沉积的脑纤维A β和认知功能障碍的TgCRND 8小鼠模型阿尔茨海默氏病，但不改变总水平的A β在大脑中。这意味着致密核心A β斑块减少约50%足以影响认知，或者疫苗接种可能调节毒性特别强的A β种类的一小部分亚群的活性/丰度。
Much evidence indicates that abnormal processing and extracellular deposition of amyloid-beta peptide (A beta), a proteolytic derivative of the beta -amyloid precursor protein (beta APP), is central to the pathogenesis of Alzheimer's disease (reviewed in ref. 1). In the PDAPP transgenic mouse model of Alzheimer's disease, immunization with Ab causes a marked reduction in burden of the brain amyloid(2,3). Evidence that A beta immunization also reduces cognitive dysfunction in murine models of Alzheimer's disease would support the hypothesis that abnormal A beta processing is essential to the pathogenesis of Alzheimer's disease, and would encourage the development of other strategies directed at the 'amyloid cascade'. Here we show that A beta immunization reduces both deposition of cerebral fibrillar A beta and cognitive dysfunction in the TgCRND8 murine model of Alzheimer's disease without, however, altering total levels of A beta in the brain. This implies that either a similar to 50% reduction in dense-cored A beta plaques is sufficient to affect cognition, or that vaccination may modulate the activity/abundance of a small subpopulation of especially toxic A beta species.