CCR6: a biomarker for Alzheimer's-like disease in a triple transgenic mouse model.
CCR6: a biomarker for Alzheimer's-like disease in a triple transgenic mouse model.
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DOI：
10.3233/jad-2010-100852
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发表时间：
2010
期刊：
影响因子：
--
通讯作者：
Offner H
中科院分区：
文献类型：
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作者：
Subramanian S;Ayala P;Wadsworth TL;Harris CJ;Vandenbark AA;Quinn JF;Offner H
阿尔茨海默病（AD）患者和动物模型的大脑炎症状态已得到广泛研究。产生 TNF-α 和 MCP-1 的活化小胶质细胞的积累促成了该疾病的病理学。然而，人们对可能导致 AD 病理的脾脏和相关外周免疫的变化知之甚少。本研究的目的是表征三重转基因 (3xTg-AD) 小鼠模型中导致 AD 样疾病发生的脾脏、血液和脑细胞群的表型和功能变化。 3xTg-AD 小鼠脑内 Gr-1+ 粒细胞、树突状细胞和巨噬细胞、脾脏和血液来源的 CD8+Ly6C+ 记忆 T 细胞和 CCR6+ B 细胞的百分比增加，分泌的 IL-6 水平也增加。与 WT 小鼠相比，12 个月大、有症状的 3xTg-AD 雌性小鼠的脑组织表现出 CCR6 mRNA 表达高度升高。重要的是，在症状前 5-6 个月大的 3xTg-AD 雌性和雄性的脑和脾组织中也检测到了 CCR6 表达的显着增加。我们的数据表明，在症状前和有症状的 3xTg-AD 小鼠的大脑和外周免疫器官中 CCR6 表达增加，强烈表明在临床 AD 样疾病发作之前存在持续的炎症过程。
The inflammatory status of the brain in patients as well as animal models of Alzheimer's disease (AD) has been extensively studied. Accumulation of activated microglia producing TNF-α and MCP-1 contribute to the pathology of the disease. However, little is known about the changes in the spleen and associated peripheral immunity that might contribute to AD pathology. The goal of this study was to characterize phenotypic and functional changes in spleen, blood and brain cell populations that contribute to development of an AD-like disease in a triple transgenic (3xTg-AD) mouse model. The 3xTg-AD mice had increased percentages of brain Gr-1+ granulocytes, dendritic cells and macrophages, spleen and blood derived CD8+Ly6C+ memory T cells and CCR6+ B cells, as well as increased levels of secreted IL-6. Brain tissue from older 12 month old symptomatic 3xTg-AD female mice exhibited highly elevated mRNA expression of CCR6 compared to WT mice. Importantly, this pronounced increase in expression of CCR6 was also detected in brain and spleen tissue from pre-symptomatic 5-6 month old 3xTg-AD females and males. Our data demonstrate increased expression of CCR6 in the brain and peripheral immune organs of both pre-symptomatic and symptomatic 3xTg-AD mice, strongly suggesting an ongoing inflammatory process that precedes onset of clinical AD-like disease.