Abnormal serum concentrations of proteins in Parkinson's disease.

Abnormal serum concentrations of proteins in Parkinson's disease.
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DOI:
10.1016/j.bbrc.2009.08.150
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发表时间:
2009-11-13
影响因子:
3.1
通讯作者:
Markopoulou K
Markopoulou K
中科院分区:
生物学4区
文献类型:
--
作者:
Goldknopf IL;Bryson JK;Strelets I;Quintero S;Sheta EA;Mosqueda M;Park HR;Appel SH;Shill H;Sabbagh M;Chase B;Kaldjian E;Markopoulou K

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使用分析验证的定量2D凝胶电泳以及单变量和多变量统计,使用血清来鉴定用于诊断帕金森病(PD)的蛋白质生物标志物。使用来自3个第一医学中心的库存样品,当与年龄匹配的正常对照(132个样品)相比时,我们在患有PD、阿尔茨海默病、肌萎缩性侧索硬化和类似神经退行性病症的患者(337个样品)的血清中鉴定了具有疾病特异性异常水平的57个特异性蛋白质斑点生物标志物。为了进一步评估它们在帕金森病中的临床有用性,我们从第二个(56个PD,30个对照)和第三个(6个PD,48个对照)医疗中心获得了前瞻性的新抽取的血清样本。通过2D-凝胶电泳评估57种生物标志物的蛋白质浓度。逐步线性判别分析选择了57个中的21个的组合作为区分PD患者和对照的最佳组合。当应用于来自第二个位点的样品时,21种蛋白质的灵敏度为93.3%(56个PD中的52个被正确分类),特异性为92.9%(30个对照中的28个被正确分类); 15个患者中的15个具有轻度症状,30个患者中的28个具有中度至重度症状,并且来自第三个位点的所有6个PD患者被正确分类。21种蛋白质中有11种在轻度症状患者中显示出统计学显著异常浓度,14种在中度至重度症状患者中显示出统计学显著异常浓度。蛋白质身份反映了帕金森病的异质性,因此可以提供监测血液的能力,用于各种PD病理生理机制:细胞变性,氧化应激,炎症和运输。
Blood serum was used to identify protein biomarkers for diagnosis of Parkinson’s disease (PD) using analytically validated quantitative 2D-gel electrophoresis, and single variable and multivariate statistics. Using banked samples from 3 first medical center, we identified 57 specific protein spot biomarkers with disease-specific abnormal levels in serum of patients with PD, Alzheimer’s disease, amyotrophic lateral sclerosis and similar neurodegenerative conditions (337 samples), when compared to age-matched normal controls (132 samples). To further assess their clinical usefulness in Parkinson’s disease, we obtained prospective newly drawn blood serum samples from a second (56 PD, 30 controls) and third (6 PD, 48 controls) medical center. The protein concentrations of the 57 biomarkers were assessed by 2D-gel electrophoresis. Stepwise linear discriminant analysis selected a combination of 21 of the 57 as optimal to distinguish PD patients from controls. When applied to the samples from the second site, the 21 proteins had sensitivity of 93.3% (52 of 56 PD correctly classified), specificity of 92.9% (28 of 30 controls correctly classified); 15 of 15 patients with mild, 28 of 30 with moderate to severe symptoms, and all of the 6 PD patients from the third site were correctly classified. Eleven of the 21 proteins showed statistically significant abnormal concentrations in patients with mild symptoms, and 14 in patients with moderate-severe symptoms. The protein identities reflect the heterogeneity of Parkinson’s disease, and thus may provide the capability of monitoring the blood for a diverse range of PD pathophysiological mechanisms: cellular degeneration, oxidative stress, inflammation, and transport.
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发表时间: 1977-01-01
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