Elevated plasma MCP-1 concentration following traumatic brain injury as a potential "predisposition" factor associated with an increased risk for subsequent development of Alzheimer's disease.
Elevated plasma MCP-1 concentration following traumatic brain injury as a potential "predisposition" factor associated with an increased risk for subsequent development of Alzheimer's disease.
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DOI：
10.3233/jad-2012-120598
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发表时间：
2012
期刊：
影响因子：
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通讯作者：
Pasinetti GM
中科院分区：
文献类型：
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作者：
Ho L;Zhao W;Dams-O'Connor K;Tang CY;Gordon W;Peskind ER;Yemul S;Haroutunian V;Pasinetti GM
我们探讨了外周血血浆蛋白表达谱的变化是否可以提供一个临床的，容易进入大脑的“窗口”，反映创伤性脑损伤（TBI）后可能导致TBI并发症的分子改变。我们招募了14名TBI和10名对照平民参与这项研究，并分析了来自20名TBI退伍军人和20名对照病例的库存血浆标本。使用抗体阵列和ELISA测定，我们探索了TBI血浆中的差异调节蛋白质种类，与来自两个独立队列的健康对照相比。我们发现了三种蛋白质生物标志物，单核细胞趋化蛋白-1（MCP-1），胰岛素样生长因子结合蛋白-3和表皮生长因子受体，它们在TBI病例的血浆标本中受到差异调节。使用所有三种蛋白质的三种生物标志物面板提供了分离TBI和对照病例的最佳潜在标准。血浆MCP-1含量与TBI的严重程度和额叶皮质中受损轴突纤维完整性指数相关。基于这些发现，我们评估了死后脑标本从7轻度认知功能障碍（MCI）和7个神经正常的情况下。我们发现MCI病例的额叶皮层MCP-1表达升高，这些病例具有患阿尔茨海默病的高风险。我们的研究结果表明，将三种生物标志物面板应用于当前的诊断标准可能会改善TBI检测，并为临床试验提供更敏感的结果指标。TBI诱导MCP-1可能是一个潜在的诱发因素，可能会增加阿尔茨海默病的发展风险。
We explored whether changes in the expression profile of peripheral blood plasma proteins may provide a clinical, readily accessible “window” into the brain, reflecting molecular alterations following traumatic brain injury (TBI) that might contribute to TBI complications. We recruited fourteen TBI and ten control civilian participants for the study, and also analyzed banked plasma specimens from 20 veterans with TBI and 20 control cases. Using antibody arrays and ELISA assays, we explored differentially-regulated protein species in the plasma of TBI compared to healthy controls from the two independent cohorts. We found three protein biomarker species, monocyte chemotactic protein-1 (MCP-1), insulin-like growth factor-binding protein-3, and epidermal growth factor receptor, that are differentially regulated in plasma specimens of the TBI cases. A three-biomarker panel using all three proteins provides the best potential criterion for separating TBI and control cases. Plasma MCP-1 contents are correlated with the severity of TBI and the index of compromised axonal fiber integrity in the frontal cortex. Based on these findings, we evaluated postmortem brain specimens from 7 mild cognitive impairment (MCI) and 7 neurologically normal cases. We found elevated MCP-1 expression in the frontal cortex of MCI cases that are at high risk for developing Alzheimer’s disease. Our findings suggest that additional application of the three-biomarker panel to current diagnostic criteria may lead to improved TBI detection and more sensitive outcome measures for clinical trials. Induction of MCP-1 in response to TBI might be a potential predisposing factor that may increase the risk for development of Alzheimer’s disease.