Decrease of TGF-β1 plasma levels and increase of nitric oxide synthase activity in leukocytes as potential biomarkers of Alzheimer's disease
Decrease of TGF-β1 plasma levels and increase of nitric oxide synthase activity in leukocytes as potential biomarkers of Alzheimer's disease
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DOI：
10.1016/s0531-5565(02)00018-9
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发表时间：
2002-06-01
影响因子：
3.9
通讯作者：
Comolli, R
中科院分区：
文献类型：
--
作者：
De Servi, B;La Porta, CAM;Comolli, R
在阿尔茨海默病（AD）患者的大脑中发现了多种炎症蛋白，包括炎症细胞因子、急性期蛋白和补体成分。在本文中，我们研究了循环炎症介质的水平作为这种疾病的潜在生物标志物，主要集中在血浆中的转化生长因子β (tgf - β 1)和白细胞中的一氧化氮合酶（NOS）活性。从48例散发性AD患者和23例相同年龄和性别的健康对照中分离血浆和白细胞。由于alpha2-Macroglobulin （alpha2M）是一种可能参与AD的急性期蛋白，是TGF-beta1活性的重要调节剂，结合并靶向该细胞因子到其适当的作用位点，我们研究了同一受试者血浆中TGF-beta1和alpha2M之间可能的复合物。结果表明，AD患者血浆中tgf - β 1水平显著降低。然而，在AD和健康的老年对照受试者中，α 2 m和tgf - β 1之间存在复合物，但无显著差异。此外，alpha2M似乎只结合这种细胞因子的无活性形式。相反，AD患者白细胞中NOS活性明显升高。因此，我们建议联合测定血浆中tgf - β 1和白细胞中NOS活性作为AD的生物标志物。(C) 2002爱思唯尔科学有限公司版权所有。
A variety of inflammatory proteins have been identified in brains of Alzheimer's disease (AD) patients, including inflammatory cytokines, acute phase proteins and complement components. In the present paper we have investigated the levels of circulating inflammatory mediators as potential biomarkers of this disease, concentrating mostly on transforming growth factor beta (TGF-beta1) in plasma and on nitric oxide synthase (NOS) activity in leukocytes. Plasma and leukocytes were isolated from 48 sporadic AD and 23 healthy control subjects of same age and sex. Since alpha2-Macroglobulin (alpha2M), an acute phase protein possibly involved in AD, is an important modulator of TGF-beta1 activity, binding and targeting this cytokine to its appropriate site of action, we have investigated the possible complex between TGF-beta1 and alpha2M in plasma of the same subjects.The results demonstrate a significant reduction of TGF-beta1 levels in plasma of AD patients. A complex between alpha2M and TGF-beta1 occurred in AD as well as healthy elderly control subjects, however, with no significant differences. Moreover, alpha2M appeared to bind only the inactive form of this cytokine. In contrast, NOS activity increased significantly in leukocytes of AD patients. Therefore, we suggest the combined determination of TGF-beta1 in the plasma and of NOS activity in the leukocytes as biomarkers of AD. (C) 2002 Elsevier Science Inc. All rights reserved.