Sustained hippocampal IL-1β overexpression mediates chronic neuroinflammation and ameliorates Alzheimer plaque pathology
Sustained hippocampal IL-1β overexpression mediates chronic neuroinflammation and ameliorates Alzheimer plaque pathology
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DOI：
10.1172/jci31450
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发表时间：
2007-06-01
影响因子：
15.9
通讯作者：
O'Banion, M. Kerry
中科院分区：
文献类型：
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作者：
Shaftel, Solomon S.;Kyrkanides, Stephanos;O'Banion, M. Kerry
神经炎症是阿尔茨海默病（AD）病理学的显著特征，并被认为有助于最终的神经退行性变。IL-1 β已经成为这种反应的主要候选者。在这里，我们描述了一种持续IL-1 β过表达的转基因小鼠模型，该模型能够在转基因激活后持续数月驱动强烈的神经炎症。这种反应的特点是星形胶质细胞和小胶质细胞活化，除了诱导促炎细胞因子。令人惊讶的是，当在AD的APPswe/PS1 dE 9小鼠模型的海马中触发时，4周的IL-1 β过表达导致淀粉样蛋白病理学的减少。嗜充血性斑块面积分数和频率以及不溶性淀粉样蛋白β 40（A β 40）和A β 42显著降低。这些结果证明了IL-1 β驱动的神经炎症在AD中可能的适应性作用，并可能有助于解释最近这种疾病的药物治疗失败。
Neuroinflammation is a conspicuous feature of Alzheimer disease (AD) pathology and is thought to contribute to the ultimate neurodegeneration that ensues. IL-1 beta has emerged as a prime candidate underlying this response. Here we describe a transgenic mouse model of sustained IL-1 beta overexpression that was capable of driving robust neuroinflammation lasting months after transgene activation. This response was characterized by astrocytic and microglial activation in addition to induction of proinflammatory cytokines. Surprisingly, when triggered in the hippocampus of the APPswe/PS1dE9 mouse model of AD, 4 weeks of IL-1 beta overexpression led to a reduction in amyloid pathology. Congophilic plaque area fraction and frequency as well as insoluble amyloid beta 40 (A beta 40) and A beta 42 decreased significantly. These results demonstrate a possible adaptive role for IL-1 beta-driven neuroinflammation in AD and may help explain recent failures of antiinflammatory therapeutics for this disease.