Decreased β-amyloid1-42 and increased tau levels in cerebrospinal fluid of patients with Alzheimer disease

Decreased β-amyloid1-42 and increased tau levels in cerebrospinal fluid of patients with Alzheimer disease
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DOI:
10.1001/jama.289.16.2094
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发表时间:
2003-04-23
影响因子:
120.7
通讯作者:
Cohen, RM
Cohen, RM
中科院分区:
医学1区
文献类型:
--
作者:
Sunderland, T;Linker, G;Cohen, RM

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背景阿尔茨海默病(AD)的特征是尸检时淀粉样斑块和tau蛋白相关神经元缠结的病理结果,但AD的临床诊断是根据病史、认知症状和排除标准确定的。寻找生前生物标志物是激烈的,并集中在脑脊液(CSF)β-淀粉样蛋白(1-42)和tau protein.Objectives比较CSF β-淀粉样蛋白和tau蛋白水平在一个新的人口AD患者和对照。对AD患者和对照组的CSF β-淀粉样蛋白和tau蛋白水平的研究进行荟萃分析。设计AD患者和对照组基线CSF β-淀粉样蛋白(1-42)和tau蛋白水平比较的横断面研究。荟萃分析涉及17项研究的CSF β-淀粉样蛋白和34项研究的CSF Tau。设置临床研究单位的国家精神卫生研究所,贝塞斯达,马里兰州的老年精神病学分支患者评估AD患者作为住院患者在美国国立卫生研究院临床中心1985年5月至2001年1月。共有203名患者参与了这项研究(131名AD患者和72名对照患者)。没有人患有其他严重疾病,131例AD病例中有31例在尸检时证实患有AD。荟萃分析提供了额外的3133例AD患者和1481名对照。主要结果测量CSF β-淀粉样蛋白(1-42)的水平通过夹心酶联免疫吸附试验与多克隆捕获抗体和单克隆检测抗体进行测量。结果AD患者CSF β-淀粉样蛋白(1-42)水平显著低于对照组(平均值[SD]为183 [121] pg/mL vs 491 [245] pg/mL; P
Context Alzheimer disease (AD) is characterized by pathological results at autopsy of amyloid plaques and tau-associated neurofibrillary tangles, but the clinical diagnosis of AD is determined on the basis of medical history, cognitive symptoms, and exclusionary criteria. The search for antemortem biomarkers is intense and has focused on cerebrospinal fluid (CSF) beta-amyloid(1-42) and tau proteins.Objectives To compare CSF beta-amyloid and tau levels in a new population of AD patients and controls. To perform a meta-analysis of studies of CSF beta-amyloid and tau levels in AD patients and controls.Design Cross-sectional study of the comparison of baseline CSF beta-amyloid(1-42) and tau levels in AD patients and controls. Meta-analysis involved 17 studies of CSF beta-amyloid and 34 studies of CSF tau.Setting Clinical research unit of the National Institute of Mental Health, Bethesda, Md.Patients The Geriatric Psychiatry Branch evaluated AD patients as inpatients at the National Institutes of Health Clinical Center between May 1985 and January 2001. A total of 203 patients participated in this study (131 with AD and 72 controls). None had other serious illnesses, and 31 of 131 AD cases had AD confirmed at autopsy. Meta-analysis provided an additional 3133 AD patients and 1481 controls.Main Outcome Measures Levels of CSF beta-amyloid(1-42) were measured by a sandwich enzyme-linked immunoabsorbent assay with a polyclonal capture antibody and a monoclonal detection antibody. Levels of CSF tau were measured with a standard commercial immunoassay.Results Levels of CSF beta-amyloid(1-42) were significantly lower in the AD patients vs controls (mean [SD], 183 [121] pg/mL vs 491 [245] pg/mL; P