Correlation of Aβ oligomer levels in matched cerebrospinal fluid and serum samples

Correlation of Aβ oligomer levels in matched cerebrospinal fluid and serum samples
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DOI:
10.1016/j.neulet.2013.06.029
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发表时间:
2013-09
影响因子:
2.5
通讯作者:
T. Kasai;T. Tokuda;M. Taylor;M. Kondo;D. Mann;Penelope G. Foulds;M. Nakagawa;D. Allsop
T. Kasai;T. Tokuda;M. Taylor;M. Kondo;D. Mann;Penelope G. Foulds;M. Nakagawa;D. Allsop
中科院分区:
医学4区
文献类型:
--
作者:
T. Kasai;T. Tokuda;M. Taylor;M. Kondo;D. Mann;Penelope G. Foulds;M. Nakagawa;D. Allsop

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我们最近报道了一种新的检测高相对分子质量淀粉样蛋白(A-β,A-β)寡聚体的酶联免疫吸附试验(EL ISA)方法,即用同一A-β单抗BAN5 0,在单抗夹心酶联免疫吸附试验(EL ISA)系统中进行捕获和检测。尽管我们之前的数据表明,这种检测方法将有助于脑脊液(CSF)样本中阿尔茨海默病(AD)的早期诊断,但侵入性脑脊液采样程序及其相关的潜在并发症限制了这些样本在常规临床实践中的使用。在这项研究中,我们已经证明了我们的ELISA可以检测到60%的血清样本和80%的非痴呆受试者的脑脊液样本中的信号。据报道,异嗜性抗体是这种类型的酶联免疫吸附试验系统中的主要混杂因素,不影响所获得的信号。尽管血清Aβ寡聚体水平出人意料地高,提示可能检测到与血清载体蛋白相关的非病理性Aβ复合体,但它们确实与匹配脑脊液样本的水平呈显著正相关。脑脊液和血清Aβ寡聚体之间的这种相关性表明,用我们的酶联免疫吸附试验测定的血清Aβ寡聚体水平可以作为反映Aβ跨血脑屏障转运的完整系统的AD的一个有用的标志物。
We recently reported a newly developed enzyme-linked immunosorbent assay (ELISA) for high molecular weight amyloid-β (Aβ) oligomers in which the same Aβ monoclonal antibody, BAN50, was used for both capture and detection in a single antibody sandwich enzyme linked immunosorbent assay (ELISA) system. Although our previous data have suggested that this assay will be useful for the early diagnosis of Alzheimer disease (AD) in cerebrospinal fluid (CSF) samples, the invasive CSF sampling procedure, with associated potential complications, limits use of these samples in routine clinical practice. In this study, we have demonstrated that our ELISA can detect signals in 60% of serum samples and in 80% of CSF samples obtained from non-demented subjects. Heterophilic antibodies that are reported to be a primary confounding factor in this type of ELISA system did not affect the signals obtained. Although the levels of serum Aβ oligomers were unexpectedly high, suggesting the possible detection of non-pathological Aβ complexes associated with serum carrier proteins, they did show a significant positive correlation with the levels obtained from matched CSF samples. This correlation between CSF and serum Aβ oligomer levels implies that the levels of serum Aβ oligomers measured with our ELISA might be useful as a marker for AD that reflects an intact system of Aβ transport across the blood brain barrier.