Measurement of apolipoprotein E (apoE) in cerebrospinal fluid

Measurement of apolipoprotein E (apoE) in cerebrospinal fluid
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DOI:
10.1023/a:1007516210548
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发表时间:
2000-04-01
影响因子:
4.4
通讯作者:
Blennow, K
Blennow, K
中科院分区:
医学3区
文献类型:
--
作者:
Hesse, C;Larsson, H;Blennow, K

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载脂蛋白 E (apoE) 是一种参与脂质运输的蛋白质,在神经损伤后的再生中发挥重要作用。因此,在研究不同形式的脑损伤以及作为大脑中正在进行的再生过程的标记时,测定脑脊液 (CSF) 中的 apoE 具有潜在的意义。然而,先前关于阿尔茨海默病(AD)中脑脊液 ApoE 的研究并未给出结论性的结果。这种不一致的结果可能与干扰样品处理和/或分析的混杂因素有关,而这些因素尚未得到充分阐明。因此,我们检查了脑脊液中 apoE 分析的不同潜在混杂因素,并开发了一种新的酶联免疫吸附测定 (ELISA)。 ApoE 的疏水特性导致其被腰椎穿刺时常用的不同类型的脑脊液收集试管吸附,导致其水平极低。这使得脑脊液处理变得至关重要,特别是在不同类型的试管中采集样本或转移到新试管中时。考虑到这些混杂因素并分析以相同方式处理的患者和对照 CSF,并使用新的 ELISA,我们可以证实我们之前的发现,即 AD 中 ApoE 水平降低(3.4 +/- 1.3 mg/l),与对照(4.5 +/- 2.7 mg/l)相比(p = 0.045)。在 AD 和对照组中,在具有 ApoE4 的个体中发现 CSF-ApoE 水平较高等位基因。我们的结果支持 AD 中 CSF-ApoE 减少,并且 CSF 的处理是一个关键因素,这可能解释了与先前研究结果不一致的原因。包含 ApoE4 等位基因的患者和对照数量的差异也可能增加不同研究之间的差异。
Apolipoprotein E (apoE) is a protein involved in transport of lipids and has been implicated to play an important role in regeneration after nerve injury. Determination of apoE in cerebrospinal fluid (CSF) thus have a potential interest when studying different forms of brain damage and as a marker of ongoing regenerative processes in the brain. However, previous studies on CSF ApoE in Alzheimer's disease (AD) have given inconclusive results. Such inconsistant results might be related to confounding factors interfering with sample handling and/or analyses, which have not been fully elucidated. We therefore examined different potential confounding factors for analyses of apoE in CSF and also developed a new enzyme linked immunosorbent assay (ELISA). The hydrophobic character of ApoE resulted in adsorbtion to different types of test tubes commonly used for collection of CSF at lumbar puncture, resulting in falsly low levels. This makes CSF handling critical, especially if samples are taken in different types of tubes, or is transferred to new tubes. Taking this confounding factors in consideration and analysing patient and control CSF handled in the same way and using the new ELISA, we could confirm our previous finding of reduced levels of ApoE in AD, (3.4 +/- 1.3mg/l) compared with controls (4.5 +/- 2.7mg/l) (p = 0.045), Both in the AD and in the control group, higher levels of CSF-ApoE was found in individuals possessing the ApoE4 alleles. Our results support that CSF-ApoE is reduced in AD, and that handling of CSF is a critical factor, which may explain the discrepant results from previous studies. Differences in the amount of patients and controls possessing the ApoE4 allele included might also increase the variance between different studies.