阿尔茨海默病和额颞叶痴呆患者脑脊液中激肽释放酶7和10浓度的改变。

Altered kallikrein 7 and 10 concentrations in cerebrospinal fluid of patients with Alzheimer's disease and frontotemporal dementia.

作者信息

Diamandis Eleftherios P, Scorilas Andreas, Kishi Tadaaki, Blennow Kaj, Luo Liu-Ying, Soosaipillai Antoninus, Rademaker Alfred W, Sjogren Magnus

机构信息

Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, and Department of Laboratory Medicine and Pathobiology, University of Toronto, Ontario, Canada.

出版信息

Clin Biochem. 2004 Mar;37(3):230-7. doi: 10.1016/j.clinbiochem.2003.11.012.

DOI:10.1016/j.clinbiochem.2003.11.012

PMID:14972646

Abstract

BACKGROUND

The role of various proteases in the pathogenesis of Alzheimer's disease is well documented. Recently, many members of the human tissue kallikrein family, a group of 15 secreted serine proteases, were found to be highly expressed in the central nervous system (CNS). Some of these enzymes can be measured in cerebrospinal fluid (CSF) by using ELISA-type methodologies.

METHODS

We quantified various kallikreins in CSF of 20 patients with Alzheimer's disease (AD), 16 patients with frontotemporal dementia (FTD), and 15 controls. We then correlated the levels of various kallikreins with presence of AD or FTD. Among all kallikreins measured, detectable levels in CSF were identified for kallikreins hK6, hK7, and hK10. Other tested kallikreins (hK5, hK8, hK11, and hK13) were unmeasurable. The most notable differences between kallikrein levels in CSF and the three groups of subjects were seen between controls and FTD patients for hK6 (decrease in FTD; P = 0.017), controls and FTD patients for hK7 (decrease in FTD; P < 0.001), and controls and AD patients for hK7 (decrease in AD; P = 0.019). In addition, significant differences were seen between FTD patients or control subjects and patients with AD patients for hK10 (increase in AD; P < 0.02). Approximately half of the AD patients had CSF hK10 levels that were higher than all patients with FTD except one and all control subjects except two. Various kallikrein concentrations in CSF were correlated, the strongest correlation seen between hK6 and hK7 (r(s) = 0.58). We also observed a statistically significant association between decreasing hK7 concentration in CSF and possession of one or two ApoE4 alleles (P = 0.014).

CONCLUSIONS

We demonstrate for the first time significant alterations of hK6, hK7, and hK10 concentration in CSF of patients with AD and FTD. Notably, all three kallikreins (hK6, hK7, and hK10) are decreased in CSF of FTD patients and hK10 is increased in CSF of AD patients, in comparison to control subjects. The possible connection between these enzymes and the pathogenesis and progression of AD and FTD needs to be further investigated.

摘要

背景

多种蛋白酶在阿尔茨海默病发病机制中的作用已有充分记录。最近，人类组织激肽释放酶家族的许多成员，一组15种分泌型丝氨酸蛋白酶，被发现于中枢神经系统（CNS）中高表达。其中一些酶可通过酶联免疫吸附测定（ELISA）类方法在脑脊液（CSF）中检测到。

方法

我们对20例阿尔茨海默病（AD）患者、16例额颞叶痴呆（FTD）患者和15名对照者的脑脊液中的多种激肽释放酶进行了定量分析。然后我们将各种激肽释放酶的水平与AD或FTD的存在情况进行关联分析。在所有检测的激肽释放酶中，脑脊液中可检测到的水平为激肽释放酶hK6、hK7和hK10。其他检测的激肽释放酶（hK5、hK8、hK11和hK13）无法测量。脑脊液中激肽释放酶水平在三组受试者之间最显著的差异见于对照组与FTD患者之间的hK6（FTD中降低；P = 0.017）、对照组与FTD患者之间的hK7（FTD中降低；P < 0.001）以及对照组与AD患者之间的hK7（AD中降低；P = 0.019）。此外，FTD患者或对照受试者与AD患者之间在hK10方面也存在显著差异（AD中升高；P < 0.02）。大约一半的AD患者脑脊液hK10水平高于除一名患者外的所有FTD患者和除两名患者外的所有对照受试者。脑脊液中各种激肽释放酶浓度之间存在相关性，hK6与hK7之间的相关性最强（r(s) = 0.58）。我们还观察到脑脊液中hK7浓度降低与携带一个或两个ApoE4等位基因之间存在统计学显著关联（P = 0.014）。