Evaluating amyloid-β oligomers in cerebrospinal fluid as a biomarker for Alzheimer's disease.

Evaluating amyloid-β oligomers in cerebrospinal fluid as a biomarker for Alzheimer's disease.
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DOI:
10.1371/journal.pone.0066381
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发表时间:
2013
期刊:
影响因子:
3.7
通讯作者:
Blennow K
Blennow K
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Hölttä M;Hansson O;Andreasson U;Hertze J;Minthon L;Nägga K;Andreasen N;Zetterberg H;Blennow K

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目前的研究评估了脑脊液中淀粉样蛋白-β寡聚体(Aβo)作为阿尔茨海默病(AD)的临床生物标志物。我们建立了一种高灵敏度的Aβo ELISA,使用相同的N端单克隆抗体(82 E1)进行捕获和检测。对AD患者、轻度认知障碍(MCI)患者和健康对照的CSF样本进行了检查。该试验对寡聚化Aβ具有特异性,定量下限为200 fg/ml,试验信号显示与合成Aβo水平密切相关。纳入了来自不同临床中心的特征良好的AD患者(n = 199)和认知健康对照(n =148)的三种临床资料,以及MCI患者(n= 165)的临床资料。      在所有3个AD-对照比较中,Aβo水平均升高,尽管与对照组存在较大重叠和分离,但远未完全分离。后来转化为AD的MCI患者的Aβo水平在组水平上增加,但几个样本的Aβo水平无法检测到。这些结果表明,CSF中存在高或可测量的Aβo水平显然与AD相关,但重叠太大,该测试本身不具有任何诊断潜力。
The current study evaluated amyloid-β oligomers (Aβo) in cerebrospinal fluid as a clinical biomarker for Alzheimer’s disease (AD). We developed a highly sensitive Aβo ELISA using the same N-terminal monoclonal antibody (82E1) for capture and detection. CSF samples from patients with AD, mild cognitive impairment (MCI), and healthy controls were examined. The assay was specific for oligomerized Aβ with a lower limit of quantification of 200 fg/ml, and the assay signal showed a tight correlation with synthetic Aβo levels. Three clinical materials of well characterized AD patients (n = 199) and cognitively healthy controls (n = 148) from different clinical centers were included, together with a clinical material of patients with MCI (n = 165). Aβo levels were elevated in the all three AD-control comparisons although with a large overlap and a separation from controls that was far from complete. Patients with MCI who later converted to AD had increased Aβo levels on a group level but several samples had undetectable levels. These results indicate that presence of high or measurable Aβo levels in CSF is clearly associated with AD, but the overlap is too large for the test to have any diagnostic potential on its own.
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