Biomarkers of inflammation and amyloid-beta phagocytosis in patients at risk of Alzheimer disease.

Biomarkers of inflammation and amyloid-beta phagocytosis in patients at risk of Alzheimer disease.
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DOI:
10.1016/j.exger.2009.08.003
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发表时间:
2010-01
影响因子:
3.9
通讯作者:
Veerhuis, Robert
Veerhuis, Robert
中科院分区:
医学2区
文献类型:
--
作者:
Fiala, Milan;Veerhuis, Robert

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诊断研究的最终目标是在神经元损伤发展之前检测阿尔茨海默病(AD)的风险。目前的淀粉样蛋白-β(Aβ)测试不能检测导致神经变性的过程。新的免疫学和蛋白质组学测试是基于CSF中炎性细胞因子和CSF或血液中其他蛋白质生物标志物以及外周血单核细胞(PBMC)的免疫生物标志物的异常出现。CSF或血液中的细胞因子、趋化因子、补体因子、血清淀粉样蛋白P成分和信号蛋白可能是诊断生物标志物的丰富来源,但这些检测的效力需要在前瞻性研究中进行检查。最近描述的缺陷Aβ吞噬作用的流式细胞术检测在不同人群(确诊的AD患者与活跃的大学教授)中检测AD患者具有高灵敏度和特异性,但在AD风险的一般人群中使用还需要进一步的经验。对Aβ“应激”的外周血单核细胞转录组的分析开始揭示特定途径与AD之间的关系。因此,新的诊断测试可以提供用于临床前检测的生物标志物,从MCI到AD的进展的澄清,以及在免疫刺激疗法的临床试验中对患者的随访。
The ultimate goal of diagnostic research is a blood test detecting the risk of Alzheimer disease (AD) before neuronal damage develops. Current amyloid-β (Aβ) tests do not detect the process leading to neurodegeneration. Novel immunologic and proteomics tests are based on aberrant appearance of inflammatory cytokines in the CSF and other protein biomarkers in the CSF or blood, and immune biomarkers of peripheral blood mononuclear cells (PBMC's). Cytokines, chemokines, complement factors, serum amyloid P component, and signaling proteins in the CSF or blood may be a rich source of diagnostic biomarkers, but the power of these tests will need to be examined in prospective studies. Recently-described flow cytometric test of defective Aβ phagocytosis detects patients with AD with a high sensitivity and specificity in distinct populations (confirmed AD patients vs. active University professors), but further experience is necessary for its use in general population at risk of AD. The analysis of the transcriptome of peripheral blood mononuclear cells “stressed” by Aβ is beginning to unravel the relations between specific pathways and AD. Thus novel diagnostic tests may provide biomarkers for pre-clinical detection, clarification of progression from MCI to AD, and follow-up of patients in clinical trials of immunostimulating therapies.
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