Elevated CSF levels of TACE activity and soluble TNF receptors in subjects with mild cognitive impairment and patients with Alzheimer's disease.
Elevated CSF levels of TACE activity and soluble TNF receptors in subjects with mild cognitive impairment and patients with Alzheimer's disease.
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DOI：
10.1186/1750-1326-6-69
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发表时间：
2011-10-06
影响因子：
15.1
通讯作者：
Shen Y
中科院分区：
文献类型：
--
作者：
Jiang H;Hampel H;Prvulovic D;Wallin A;Blennow K;Li R;Shen Y
我们最近报道，肿瘤坏死因子（TNF）受体，TNFR 1和TNFR 2，表达水平显着改变，在脑和脑脊液（CSF）与阿尔茨海默病（AD）。此外，我们还发现，在阿尔茨海默病小鼠模型中，TNF受体（TNFR 1）的遗传缺失通过β-分泌酶（BACE 1）调节减少淀粉样蛋白斑块和淀粉样蛋白β肽（Aβ）的产生。TNF-α转化酶（TACE/ADAM-17）不仅能裂解TNF-α前体，还能裂解TNF-α受体，但其活性是否改变尚不清楚。在这项研究中，我们检查了32名AD患者和27名年龄匹配的健康对照（HC）的CSF中的TACE。有趣的是，我们发现与HC相比，AD患者CSF中的TACE活性显著升高。此外，我们还测定了相同患者中TACE裂解的可溶性形式的TNFR 1和TNFR 2的CSF水平。我们发现，与年龄和性别匹配的健康对照组相比，AD患者CSF中TACE裂解的可溶性TNFR 1（sTNFR 1）和TNFR 2（sTNFR 2）水平更高。sTNFR 1与sTNFR 2水平高度相关（rs = 0.567-0.663，p < 0.01）。sTNFR 1、sTNFR 2水平与TACE活性显著相关（rs = 0.491-0.557，p < 0.05）。为了检查TACE活性和裂解的可溶性TNFR水平的变化是否是AD过程中的早期事件，我们测量了47名轻度认知障碍（MCI）受试者CSF中的这些分子，MCI被认为是AD的临床前阶段。出乎意料的是，我们发现MCI组的TACE活性和可溶性TNFR水平显着高于AD患者。这些结果表明，TACE活性和可溶性TNF受体可能是AD和MCI的潜在诊断候选生物标志物。
We recently reported that expression levels of tumor necrosis factor (TNF) receptors, TNFR1 and TNFR2, are significantly changed in the brains and cerebrospinal fluid (CSF) with Alzheimer's disease (AD). Moreover, we also found that, in an Alzheimer's mouse model, genetic deletion of TNF receptor (TNFR1) reduces amyloid plaques and amyloid beta peptides (Aβ) production through β-secretase (BACE1) regulation. TNF-α converting enzyme (TACE/ADAM-17) does not only cleave pro- TNF-α but also TNF receptors, however, whether the TACE activity was changed in the CSF was not clear. In this study, we examined TACE in the CSF in 32 AD patients and 27 age-matched healthy controls (HCs). Interestingly, we found that TACE activity was significantly elevated in the CSF from AD patients compared with HCs. Furthermore, we also assayed the CSF levels of TACE cleaved soluble forms of TNFR1 and TNFR2 in the same patients. We found that AD patients had higher levels of both TACE cleaved soluble TNFR1 (sTNFR1) and TNFR2 (sTNFR2) in the CSF compared to age- and gender-matched healthy controls. Levels of sTNFR1 correlated strongly with the levels of sTNFR2 (rs = 0.567-0.663, p < 0.01). The levels of both sTNFR1 and sTNFR2 significantly correlated with the TACE activity (rs = 0.491-0.557, p < 0.05). To examine if changes in TACE activity and in levels of cleaved soluble TNFRs are an early event in the course of AD, we measured these molecules in the CSF from 47 subjects with mild cognitive impairment (MCI), which is considered as a preclinical stage of AD. Unexpectedly, we found significantly higher levels of TACE activity and soluble TNFRs in the MCI group than that in AD patients. These results suggest that TACE activity and soluble TNF receptors may be potential diagnostic candidate biomarkers in AD and MCI.
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影响因子：
4.8
作者：
Buxbaum, JD;Liu, KN;Black, RA
通讯作者：
Black, RA
DOI：
10.1073/pnas.96.7.3922
发表时间：
1999-03-30
影响因子：
11.1
作者：
Lammich, S;Kojro, E;Fahrenholz, F
通讯作者：
Fahrenholz, F
DOI：
10.1083/jcb.200705042
发表时间：
2007-08-27
期刊：
The Journal of cell biology
影响因子：
--
作者：
He P;Zhong Z;Lindholm K;Berning L;Lee W;Lemere C;Staufenbiel M;Li R;Shen Y
通讯作者：
Shen Y
影响因子：
3.8
作者：
Ermert, M;Pantazis, C;Ermert, L
通讯作者：
Ermert, L
影响因子：
3.5
作者：
DYRKS, T;MONNING, U;TURNER, J
通讯作者：
TURNER, J