A specific enzyme-linked immunosorbent assay for measuring beta-amyloid protein oligomers in human plasma and brain tissue of patients with Alzheimer disease.
A specific enzyme-linked immunosorbent assay for measuring beta-amyloid protein oligomers in human plasma and brain tissue of patients with Alzheimer disease.
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一种特定的酶联免疫吸附测定法，用于测量患有阿尔茨海默氏病患者的人血浆和脑组织中β-淀粉样蛋白低聚物。
DOI：
10.1001/archneurol.2008.565
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发表时间：
2009-02
影响因子：
--
通讯作者：
Selkoe, Dennis J.
中科院分区：
文献类型：
--
作者：
Xia, Weiming;Yang, Ting;Shankar, Ganesh;Smith, Imelda M.;Shen, Yong;Walsh, Dominic M.;Selkoe, Dennis J.
为了检测家族性阿尔茨海默病(AD)患者和家族性阿尔茨海默病(AD)患者血浆和脑组织中A-β的表达水平，建立了一种新的针对A-β寡聚体的酶联免疫吸附试验(EL ISA)。用相同的N-末端A-β抗体进行抗原捕获和检测，建立了OA-β酶联免疫吸附试验。用常规单体Aβ和新的OAβELISA对AD和对照组的血浆和死后脑进行了系统分析。我们检测了36例临床特征良好的AD患者和10名对照的血浆样本中的OAβ种类。此外，9名确诊的AD患者和7名对照受试者的尸检样本均为尸检样本。用合成的二硫键Aβ1-40Ser26Cys二聚体验证了OAβELISA的特异性，该二聚体在β-巯基乙醇中解离之前而不是在二聚体解离后被特异性检测。血浆分析显示，在所有受试者中，相对的OAβ水平与相对Aβ42单体水平密切相关。对一部分AD患者，包括一名由早老素突变引起的AD患者的连续血浆样本的分析显示，在1-2年的时间里，OAβ和Aβ42单体水平下降。在9例AD患者和7例对照组的脑组织中，AD患者的OAβ和单体Aβ42均持续升高。OAβ特异性ELISA法揭示了血浆和脑中OAβ和Aβ42单体水平之间的紧密联系，这两种形式在血浆中都会随着时间的推移而下降，可能反映了它们在大脑中的不溶性增加。
A new ELISA specific for oligomeric assemblies of amyloid β protein (oAβ) was developed to examine in vivo levels of oAβ vs. monomeric Aβ in sporadic and familial Alzheimer disease (AD) plasma and brain tissue. To establish the oAβ ELISA, the same N-terminal Aβ antibody was used for antigen capture and detection. Plasmas and postmortem brains from AD and control subjects were systematically analyzed by conventional monomeric Aβ and new oAβ ELISAs. We measured oAβ species in plasma samples from 36 clinically well-characterized AD patients and 10 controls. In addition, postmortem samples were obtained from brain autopsies of 9 verified AD and 7 control subjects. The specificity of oAβ ELISA was validated with a disulfide crossed-linked, synthetic Aβ1–40Ser26Cys dimer that was specifically detected before but not after the dissociation of the dimers in β-mercaptoethanol. Plasma assays showed that relative oAβ levels were closely associated with relative Aβ42 monomer levels across all subjects. Analysis of sequential plasma samples from a subset of the AD patients, including a patient with AD caused by a presenilin mutation, revealed decreases in both oAβ and Aβ42 monomer levels over a 1–2 year period. In brain tissue from 9 AD and 7 control subjects, both oAβ and monomeric Aβ42 were consistently higher in the AD cases. An oAβ-specific ELISA reveals a tight link between oAβ and Aβ42 monomer levels in plasma and brain, and both forms can decline over time in plasma, presumably reflecting their increasing insolubility in the brain.
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影响因子：
9.9
作者：
Ringman, J. M.;Younkin, S. G.;Cummings, J. L.
通讯作者：
Cummings, J. L.
影响因子：
14.5
作者：
Hye, A.;Lynham, S.;Lovestone, S.
通讯作者：
Lovestone, S.
影响因子：
9.9
作者：
Ertekin-Taner, N.;Younkin, L. H.;Graff-Radford, N. R.
通讯作者：
Graff-Radford, N. R.
影响因子：
4.8
作者：
Lee, EB;Leng, LZ;Lee, VMY
通讯作者：
Lee, VMY
DOI：
10.1073/pnas.0409336102
发表时间：
2005-02-15
影响因子：
11.1
作者：
Georganopoulou, DG;Chang, L;Mirkin, CA
通讯作者：
Mirkin, CA