Age but not diagnosis is the main predictor of plasma amyloid β-protein levels

Age but not diagnosis is the main predictor of plasma amyloid β-protein levels
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DOI:
10.1001/archneur.60.7.958
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发表时间:
2003-07-01
影响因子:
--
通讯作者:
Irizarry, MC
Irizarry, MC
中科院分区:
其他
文献类型:
--
作者:
Fukumoto, H;Tennis, M;Irizarry, MC

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背景:在家族性阿尔茨海默病(AD)突变患者中,血浆淀粉样β蛋白Abeta42水平升高,据报道,高水平的患者被认为是发展为AD的高危个体。目的:确定散发性AD患者血浆Abeta40和Abeta42水平是否有特征性变化,并在具有前瞻性特征的门诊人群中检测血浆Abeta40和Abeta42水平与临床、人口学和遗传变量的关系。患者:共有371名散发性AD患者(n=146),轻度认知障碍(n=37),方法:收集96例帕金森病患者和92例非痴呆者的血浆标本,用夹心酶联免疫吸附试验检测Abeta40和Abeta42的水平,用捕获抗体BNT77(抗Abeta11-28)和检测抗体BA27(抗Abeta40)和BC05(抗Abeta42)检测Abeta40和Abeta42水平。当随年龄变化时,Abeta40和Abeta42的平均血浆水平在4个诊断组之间没有显著差异。在轻度认知损害和AD组中,Abeta40和Abeta42水平与记忆损害的持续时间或认知测试分数无关。Abeta测定不受AD家族史、载脂蛋白E基因分型、胆碱酯酶抑制剂、维生素E、他汀类药物、非类固醇抗炎药或雌激素使用情况的影响。结论:血浆Abeta测定随着年龄的增长而增加,但与家族性AD的报道不同,血浆Abeta测定对轻度认知损害或散发性AD的临床诊断既不敏感也不特异。
Background: Plasma amyloid beta-protein Abeta42 levels are increased in patients with familial Alzheimer disease (AD) mutations, and high levels reportedly identify individuals at risk to develop AD.Objectives: To determine whether there are characteristic changes in plasma Abeta40 and Abeta42 levels in sporadic AD, and to examine the relationship of plasma Abeta measures with clinical, demographic, and genetic variables in a prospectively characterized outpatient clinic population.Patients: A total of 371 outpatients with sporadic AD (n = 146), mild cognitive impairment (n = 37), or Parkinson disease (n = 96) and nondemented control cases (n = 92).Methods: We collected plasma samples and determined Abeta40 and Abeta42 levels by sandwich enzyme-linked immunosorbent assay with the use of the capture antibody BNT77 (anti-Abeta11-28) and the detector anti-bodies horseradish peroxidase-linked BA27 (anti-Abeta40) and BC05 (anti-Abeta42).Results: Mean Abeta40 and Abeta42 levels increased significantly with age in each diagnostic group. When covaried for age, mean plasma levels of Abeta40 and Abeta42 did not differ significantly among the 4 diagnostic groups. Within the mild cognitive impairment and AD groups, Abeta40 and Abeta42 levels did not correlate with duration of memory impairment or with cognitive test scores. The Abeta measures were not influenced by family history of AD, apolipoprotein E genotype, or current medication use of cholinesterase inhibitors, vitamin E, statins, nonsteroidal anti-inflammatory drugs, or estrogen.Conclusions: Plasma Abeta measures increase with age, but, in contrast to reports on familial AD, plasma Abeta measures were neither sensitive nor specific for the clinical diagnosis of mild cognitive impairment or sporadic AD.