Measurement of gelatinase B (MMP-9) in the cerebrospinal fluid of patients with vascular dementia and Alzheimer disease

Measurement of gelatinase B (MMP-9) in the cerebrospinal fluid of patients with vascular dementia and Alzheimer disease
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DOI:
10.1161/01.str.0000127420.10990.76
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发表时间:
2004-06-01
期刊:
影响因子:
8.3
通讯作者:
Rosenberg, GA
Rosenberg, GA
中科院分区:
医学1区
文献类型:
--
作者:
Adair, JC;Charlie, J;Rosenberg, GA

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背景和目的:由于人口老龄化,血管性痴呆的重要性日益增加。生物标志物对区分血管性痴呆(VaD)和阿尔茨海默病(AD)具有重要意义。由于脑血管疾病会增加脑基质金属蛋白酶(MMPs)和组织金属蛋白酶抑制剂(TIMPs)的表达,我们假设VaD患者脑脊液中MMPs会升高,而AD患者则不会升高。方法:选取15例VaD患者,包括多发梗死性痴呆和小脑血管疾病引起的进行性痴呆。患者随访4至10年以确认诊断。对30例AD患者也进行了研究。患者在初始评估时收集脑脊液。明胶酶A (MMP-2)和明胶酶B (MMP-9)用明胶底物酶谱法测定,TIMPs用反向酶谱法测定。对照脑脊液取自神经正常受试者。结果:VaD患者脑脊液中mmp -9水平明显高于AD患者(P
Background and Purpose-Vascular causes of dementia are increasing in importance because of the aging of the population. Biological markers to distinguish patients with vascular dementia (VaD) from Alzheimer disease (AD) would be very useful. Because cerebrovascular disease increases expression of brain matrix metalloproteinases (MMPs) and tissue inhibitors to metalloproteinases (TIMPs), we hypothesized that MMPs would be elevated in the cerebrospinal fluid (CSF) of patients with VaD, but not in patients with AD.Methods-Fifteen patients with VaD were identified, including dementia caused by multiple infarcts and progressive dementia caused by disease of the small cerebral blood vessels. Patients were followed-up for 4 to 10 years to confirm the diagnosis. Thirty patients with AD were also studied. Patients had CSF collected at their initial evaluation. Gelatinase A (MMP-2) and gelatinase B (MMP-9) were quantified by gelatin-substrate zymography, and TIMPs were measured by reverse zymography. Control CSF was obtained from neurologically normal subjects.Results-MMP-9 levels were significantly elevated in the CSF of VaD patients compared either to those with AD (P