Alzheimer’s disease (AD) is the most common cause of dementia and most of AD patients suffer from vascular abnormalities and neuroinflammation. There is an urgent need to develop novel blood biomarkers capable of diagnosing Alzheimer’s disease (AD) at very early stage. This study was performed to find out new accurate plasma diagnostic biomarkers for AD by investigating a direct relationship between plasma contact system and AD. A total 101 of human CSF and plasma samples from normal and AD patients were analyzed. The contact factor activities in plasma were measured with the corresponding specific peptide substrates. The activities of contact factors (FXIIa, FXIa, plasma kallikrein) and FXa clearly increased and statistically correlated as AD progresses. We present here, for the first time, the FXIIa cut-off scores to as: > 26.3 U/ml for prodromal AD [area under the curve (AUC) = 0.783, p < 0.001] and > 27.2 U/ml for AD dementia (AUC = 0.906, p < 0.001). We also describe the cut-off scores from the ratios of CSF Aβ1–42 versus the contact factors. Of these, the representative ratio cut-off scores of Aβ1–42/FXIIa were to be: < 33.8 for prodromal AD (AUC = 0.965, p < 0.001) and < 27.44 for AD dementia (AUC = 1.0, p < 0.001). The activation of plasma contact system is closely associated with clinical stage of AD, and FXIIa activity as well as the cut-off scores of CSF Aβ1–42/FXIIa can be used as novel accurate diagnostic AD biomarkers.

中文翻译：

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血浆接触因子作为诊断阿尔茨海默氏病的新型生物标志物

阿尔茨海默氏病（AD）是痴呆症的最常见病因，大多数AD患者患有血管异常和神经炎症。迫切需要开发能够在非常早期阶段诊断阿尔茨海默氏病（AD）的新型血液生物标记物。通过研究血浆接触系统和AD之间的直接关系，进行本研究以发现新的准确的AD血浆诊断生物标志物。共分析了来自正常和AD患者的101例人CSF和血浆样品。用相应的特异性肽底物测量血浆中的接触因子活性。随着AD的进展，接触因​​子（FXIIa，FXIa，血浆激肽释放酶）和FXa的活性明显增加并且在统计学上相关。我们第一次在这里展示FXIIa的截止分数是：> 26。前驱AD [曲线下面积（AUC）= 0.783，p <0.001]为3 U / ml，AD痴呆> AUC = 27.2 U / ml（AUC = 0.906，p <0.001）。我们还根据脑脊液Aβ1-42与接触因子之比来描述临界值。其中，Aβ1-42/ FXIIa的代表性比率截止得分为：前驱性AD的<33.8（AUC = 0.965，p <0.001）和AD痴呆的<27.44（AUC = 1.0，p <0.001）。血浆接触系统的激活与AD的临床阶段密切相关，FXIIa的活性以及CSFAβ1-42/ FXIIa的临界值可以用作新型准确的AD诊断生物标志物。其中，Aβ1-42/ FXIIa的代表性比率截止得分为：前驱性AD的<33.8（AUC = 0.965，p <0.001）和AD痴呆的<27.44（AUC = 1.0，p <0.001）。血浆接触系统的激活与AD的临床阶段密切相关，FXIIa的活性以及CSFAβ1-42/ FXIIa的临界值可以用作新型准确的AD诊断生物标志物。其中，Aβ1-42/ FXIIa的代表性比率截止得分为：前驱性AD的<33.8（AUC = 0.965，p <0.001）和AD痴呆的<27.44（AUC = 1.0，p <0.001）。血浆接触系统的激活与AD的临床阶段密切相关，FXIIa的活性以及CSFAβ1-42/ FXIIa的临界值可以用作新型准确的AD诊断生物标志物。