Identification of novel biomarker candidates by differential peptidomics analysis of cerebrospinal fluid in Alzheimer's disease.

Identification of novel biomarker candidates by differential peptidomics analysis of cerebrospinal fluid in Alzheimer's disease.
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DOI:
10.2174/138620705774962391
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发表时间:
2005-11
影响因子:
1.8
通讯作者:
H. Selle;J. Lamerz;K. Buerger;A. Dessauer;K. Hager;H. Hampel;J. Karl;M. Kellmann;L. Lannfelt;J. Louhija;M. Riepe;W. Rollinger;H. Tumani;M. Schrader;H. Zucht
H. Selle;J. Lamerz;K. Buerger;A. Dessauer;K. Hager;H. Hampel;J. Karl;M. Kellmann;L. Lannfelt;J. Louhija;M. Riepe;W. Rollinger;H. Tumani;M. Schrader;H. Zucht
中科院分区:
医学4区
文献类型:
--
作者:
H. Selle;J. Lamerz;K. Buerger;A. Dessauer;K. Hager;H. Hampel;J. Karl;M. Kellmann;L. Lannfelt;J. Louhija;M. Riepe;W. Rollinger;H. Tumani;M. Schrader;H. Zucht

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这项工作的目的是应用肽组学技术检测和鉴定阿尔茨海默病(AD)的可靠和强大的生物标志物,有助于促进和进一步提高阿尔茨海默病的诊断。采用一种新的多肽综合对比分析方法,对来自AD患者、认知未受损受试者和其他原发性痴呆患者的312份脑脊液(CSF)样本作为四个独立的分析集进行分析。通过结合交叉验证程序,根据其辨别能力从总共6000多个不同的肽信号中选择候选信号。利用质谱技术鉴定出12个候选片段,可能是神经保护神经内分泌蛋白VGF的片段,另一个是补体因子C3后代C3f。结合肽谱分析和交叉验证,发现了新的潜在生物标志物,具有显著的稳健性,与阿尔茨海默病的病理生理密切相关。
The objective of this work was the application of peptidomics technologies for the detection and identification of reliable and robust biomarkers for Alzheimer's disease (AD) contributing to facilitate and further improve the diagnosis of AD. Using a new method for the comprehensive and comparative profiling of peptides, the differential peptide display (DPD), 312 cerebrospinal fluid (CSF) samples from AD patients, cognitively unimpaired subjects and from patients suffering from other primary dementia disorders were analysed as four independent analytical sets. By combination with a cross validation procedure, candidates were selected from a total of more than 6,000 different peptide signals based on their discriminating power. Twelve candidates were identified using mass-spectrometric techniques as fragments of the possibly neuroprotective neuroendocrine protein VGF and another one as the complement factor C3 descendent C3f. The combination of peptide profiling and cross validation resulted in the detection of novel potential biomarkers with remarkable robustness and a close relation to AD pathophysiology.