The load of amyloid-β oligomers is decreased in the cerebrospinal fluid of Alzheimer's disease patients.
The load of amyloid-β oligomers is decreased in the cerebrospinal fluid of Alzheimer's disease patients.
复制标题
阿尔茨海默氏病患者脑脊液中淀粉样蛋白-β 寡聚物的负荷减少。
DOI：
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发表时间：
2012
期刊：
影响因子：
--
通讯作者：
G. Sancesario
中科院分区：
文献类型：
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作者：
G. Sancesario;M. T. Cencioni;Z. Esposito;G. Borsellino;M. Nuccetelli;A. Martorana;L. Battistini;R. Sorge;G. Spalletta;D. Ferrazzoli;G. Bernardi;S. Bernardini;G. Sancesario
β淀粉样蛋白（Aβ）低聚物是分子量可变的不均匀和不稳定的化合物。流式细胞术和基于荧光共振能量转移（FRET）的方法允许同时检测天然形式的低分子量和高分子量Aβ寡聚体。我们评估了在用或不用RIPA缓冲液稀释的脑脊液（CSF）中估计不同种类的Aβ寡聚体是否比测量Aβ42单体、总tau（t-tau）和磷酸化tau（p-tau）更有助于诊断阿尔茨海默病（AD）。与其他痴呆（OD）（n = 35）或其他神经系统疾病（OND）（n = 56）患者相比，AD患者（n = 46）CSF中检测到t-tau（p <0.01）和p-tau（p <0.01）增加，Aβ42（p < 0.01）减少。在天然CSF（n = 137）中，AD患者Aβ寡聚体水平低于OD和OND患者（p < 0.05）;此外，AD患者Aβ寡聚体/p-tau比值低于OD（p < 0.01）和OND（p < 0.05）患者，灵敏度为75%，特异性为64%。然而，在用RIPA稀释的CSF中（n = 30），AD患者的Aβ寡聚体似乎高于OND患者（p < 0.05），表明它们在RIPA后部分解聚，更容易检测。总之，天然CSF中的FRET分析对于正确确定Aβ寡聚体的组成至关重要。在该实验环境中，同时估计低分子量和高分子量Aβ寡聚体与其他生物标志物在AD诊断中一样有用。在AD的天然CSF中检测到的少量Aβ寡聚体可能与其在脑中的水平呈负相关，如Aβ单体所发生的那样，Aβ单体代表淀粉样蛋白致病级联的生物标志物。
Amyloid-β (Aβ) oligomers are heterogeneous and instable compounds of variable molecular weight. Flow cytometry and fluorescence resonance energy transfer (FRET)-based methods allow the simultaneous detection of Aβ oligomers with low and high molecular weight in their native form. We evaluated whether an estimate of different species of Aβ oligomers in the cerebrospinal fluid (CSF) with or without dilution with RIPA buffer could be more useful in the diagnosis of Alzheimer's disease (AD) than the measurement of Aβ42 monomers, total tau (t-tau), and phosphorylated tau (p-tau). Increased t-tau (p < 0.01) and p-tau (p < 0.01), and decreased Aβ42 (p < 0.01), were detected in the CSF of patients with AD (n = 46), compared to patients with other dementia (OD) (n = 35) or with other neurological disorders (OND) (n = 56). In native CSF (n = 137), the levels of Aβ oligomers were lower (p < 0.05) in AD than in OD and OND patients; in addition, the ratio Aβ oligomers/p-tau was lower in AD than in OD (p < 0.01) and OND (p < 0.05) patients, yielding a sensitivity of 75% and a specificity of 64%. However, in CSF diluted with RIPA (n = 30), Aβ oligomers appeared higher (p < 0.05) in AD than in OND patients, suggesting they become partially disaggregated and more easily detectable after RIPA. In conclusion, FRET analysis in native CSF is essential to correctly determine the composition of Aβ oligomers. In this experimental setting, the simultaneous estimate of low and high molecular weight Aβ oligomers is as useful as the other biomarkers in the diagnosis of AD. The low amount of Aβ oligomers detected in native CSF of AD may be inversely related to their levels in the brain, as occurs for Aβ monomers, representing a biomarker for the amyloid pathogenic cascade.
影响因子：
9.9
作者：
R. Faber
通讯作者：
R. Faber
DOI：
10.3233/jad-2010-1397
发表时间：
2010
期刊：
Journal of Alzheimer's disease : JAD
影响因子：
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作者：
Head E;Pop V;Sarsoza F;Kayed R;Beckett TL;Studzinski CM;Tomic JL;Glabe CG;Murphy MP
通讯作者：
Murphy MP