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轻度认知障碍和各类痴呆患者脑脊液中17β-羟类固醇脱氢酶10的水平

Levels of 17β-Hydroxysteroid Dehydrogenase Type 10 in Cerebrospinal Fluid of People with Mild Cognitive Impairment and Various Types of Dementias.

作者信息

Kristofikova Zdena, Ricny Jan, Vyhnalek Martin, Hort Jakub, Laczo Jan, Sirova Jana, Klaschka Jan, Ripova Daniela

机构信息

National Institute of Mental Health, Klecany, Czech Republic.

Memory Disorders Clinic, Department of Neurology, 2nd Faculty of Medicine, Charles University in Prague and Motol University Hospital, Prague 5, Czech Republic.

出版信息

J Alzheimers Dis. 2015;48(1):105-14. doi: 10.3233/JAD-142898.

Abstract

BACKGROUND

Overexpression of the mitochondrial enzyme 17β-hydroxysteroid dehydrogenase type 10 (17β-HSD10, which is also known as the intracellular amyloid-β peptide (Aβ) binding protein) is observed in cortical or hippocampal regions of patients with Alzheimer's disease (AD). It appears that 17β-HSD10 may play a role in the pathogenesis of AD.

OBJECTIVE

We investigated the possibility that levels of 17β-HSD10 in cerebrospinal fluid could be a prospective biomarker of AD.

METHODS

We estimated the enzyme levels in 161 people (15 non-demented controls, 52 people with mild cognitive impairment (MCI), 35 people with probable AD, or 59 people with other types of dementia) and compared them with those of Aβ(1- 42), tau, and phospho-tau.

RESULTS

We found significantly higher levels of 17β-HSD10 in people with MCI due to AD (to 109.9% ), with AD (to 120.0% ), or with other types of dementia (to 110.9% ) when compared to the control group. The sensitivity of the new biomarker to AD was 80.0% , and the specificity was 73.3% (compared to controls) or 52.5-59.1% (compared to other types of dementia). Results of multiple linear regression and of correlation analysis revealed AD-mediated changes in links between 17β-HSD10 and Mini Mental State Examination score.

CONCLUSION

It seems that changes in 17β-HSD10 start many years before symptom onset, analogous to those in Aβ1 - 42, tau, or phospho-tau and that the levels are a relatively highly sensitive but unfortunately less specific biomarker of AD. A role of 17β-HSD10 overexpression in AD is discussed.

摘要

背景

在阿尔茨海默病(AD)患者的皮质或海马区域观察到线粒体酶17β-羟类固醇脱氢酶10(17β-HSD10,也称为细胞内淀粉样β肽(Aβ)结合蛋白)的过表达。17β-HSD10似乎在AD的发病机制中起作用。

目的

我们研究了脑脊液中17β-HSD10水平可能作为AD前瞻性生物标志物的可能性。

方法

我们估计了161人(15名非痴呆对照者、52名轻度认知障碍(MCI)患者、35名可能患有AD的患者或59名患有其他类型痴呆的患者)的酶水平,并将其与Aβ(1-42)、tau和磷酸化tau的水平进行比较。

结果

我们发现,与对照组相比,因AD导致MCI的患者、患有AD的患者或患有其他类型痴呆的患者中17β-HSD10水平显著更高(分别高达109.9%、120.0%和110.9%)。这种新生物标志物对AD的敏感性为80.0%,特异性为73.3%(与对照组相比)或52.5%-59.1%(与其他类型痴呆相比)。多元线性回归和相关分析结果显示,AD介导了17β-HSD10与简易精神状态检查评分之间联系的变化。

结论

17β-HSD10的变化似乎在症状出现前很多年就开始了,类似于Aβ1-42、tau或磷酸化tau的变化,并且其水平是AD相对高度敏感但遗憾的是特异性较低的生物标志物。文中讨论了17β-HSD10过表达在AD中的作用。

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