脑脊液中β-分泌酶（BACE1）水平作为轻度认知障碍风险的预测指标。

Levels of beta-secretase (BACE1) in cerebrospinal fluid as a predictor of risk in mild cognitive impairment.

作者信息

Zhong Zhenyu, Ewers Michael, Teipel Stefan, Bürger Katharina, Wallin Anders, Blennow Kaj, He Ping, McAllister Carrie, Hampel Harald, Shen Yong

机构信息

Haldeman Laboratory of Molecular and Cellular Neurobiology, Sun Health Research Institute, Sun City, AZ 85351, USA.

出版信息

Arch Gen Psychiatry. 2007 Jun;64(6):718-26. doi: 10.1001/archpsyc.64.6.718.

DOI:10.1001/archpsyc.64.6.718

PMID:17548753

Abstract

CONTEXT

Elevated beta-secretase (beta-site amyloid precursor protein-cleaving enzyme 1 [BACE1]) activity has been found in the brains of patients with sporadic Alzheimer disease (AD) compared with controls. Now we are particularly interested in whether BACE1 can be identified in the cerebrospinal fluid (CSF) of patients with mild cognitive impairment (MCI), a population at high risk for AD. The possible presence of BACE1 in the CSF of patients with AD and MCI has so far gone unreported.

OBJECTIVE

To examine whether BACE1 can be identified in the CSF of patients with MCI.

DESIGN

We evaluated CSF BACE1 levels using 2 sandwich enzyme-linked immunosorbent assays, BACE1 enzymatic activities by means of synthetic fluorescence substrate, and total amyloid-beta peptide levels using a sandwich enzyme-linked immunosorbent assay.

SETTING

Two independent research centers.

PARTICIPANTS

Eighty patients with sporadic AD, 59 patients with MCI, and 69 controls.

MAIN OUTCOME MEASURES

BACE1 levels and enzymatic activities and amyloid-beta peptide levels.

RESULTS

Increased CSF levels of BACE1 protein were associated with increased risk ratios (RRs) for patients with MCI compared with controls (RR, 2.08; 95% confidence interval [CI], 1.58-2.58) and patients with AD (RR, 1.65; 95% CI, 1.19-2.03). Similarly, patients with MCI showed increased levels of BACE1 activity compared with controls (RR, 2.17; 95% CI, 1.66-2.71) and patients with AD (RR, 3.71; 95% CI, 2.74-4.36). For total amyloid-beta peptide and tau, increased CSF levels were associated with a higher risk of MCI compared with controls. The BACE1 activity was significantly correlated with BACE1 protein level (rho = 0.23; P<.001) and amyloid-beta peptide level (rho = 0.39; P<.001), with amyloid-beta peptide correlated with BACE1 protein level (rho = 0.30; P<.001).

CONCLUSION

Significant elevation of BACE1 levels and activity in CSF is an indicator of MCI, which could be an early stage of AD.

摘要

背景

与对照组相比，散发性阿尔茨海默病（AD）患者大脑中的β-分泌酶（β-位点淀粉样前体蛋白裂解酶1 [BACE1]）活性升高。现在我们特别感兴趣的是，在轻度认知障碍（MCI）患者的脑脊液（CSF）中是否能检测到BACE1，MCI患者是AD的高危人群。AD和MCI患者脑脊液中可能存在BACE1这一情况迄今尚未见报道。

目的

检测MCI患者脑脊液中是否能检测到BACE1。

设计

我们使用两种夹心酶联免疫吸附测定法评估脑脊液BACE1水平，通过合成荧光底物检测BACE1酶活性，并使用夹心酶联免疫吸附测定法检测总淀粉样β肽水平。

地点

两个独立的研究中心。

参与者

80例散发性AD患者、59例MCI患者和69例对照组。

主要观察指标

BACE1水平、酶活性和淀粉样β肽水平。

结果

与对照组（风险比[RR]，2.08；95%置信区间[CI]，1.58 - 2.58）和AD患者（RR，1.65；95% CI，1.19 - 2.03）相比，MCI患者脑脊液中BACE1蛋白水平升高与风险比增加相关。同样，与对照组（RR，2.17；95% CI，1.66 - 2.71）和AD患者（RR，3.71；95% CI，2.74 - 4.36）相比，MCI患者的BACE1活性水平升高。对于总淀粉样β肽和tau，与对照组相比，脑脊液水平升高与MCI风险更高相关。BACE1活性与BACE1蛋白水平显著相关（rho = 0.23；P <.001）和淀粉样β肽水平（rho = 0.39；P <.001），淀粉样β肽与BACE1蛋白水平相关（rho = 0.30；P <.001）。