A novel peptidomics approach to detect markers of Alzheimer鈥檚 disease in cerebrospinal fluid

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• 作者：Dorien Wijte^a ; ¹ ; Liam A. McDonnell^a ; Crina I.A. Balog^a ; Koen Bossers^b ; André ; M. Deelder^a ; Dick F. Swaab^b ; Joost Verhaagen^b ; Oleg A. Mayboroda^a ; ^{o.a.mayboroda@lumc.nl}
• 关键词：Alzheimer&rsquo ; s disease ; Peptidomics ; Cerebrospinal fluid ; Endogenous peptides
• 刊名：Methods
• 出版年：2012
• 期刊代码：103_10462023
• 类别：imm
• 出版时间：April, 2012
• 卷：56
• 期：4
• 页码：500-507
• 文件大小：1239 K

摘要

Sensitive and specific diagnosis and monitoring of disease progression are of prime importance to develop new therapies for Alzheimer鈥檚 disease patients. Although the diagnostic accuracy, verified by pathological examination is high, it is currently not possible to diagnose Alzheimer鈥檚 disease with a high degree of certainty until relatively late in the disease process. Here, we have undertaken a peptidome analysis of postmortem cerebrospinal fluid of neuropathologically confirmed Alzheimer鈥檚 disease patients and non-demented controls using a combination of methods and technologies. This includes novel sample preparation based on the enrichment of endogenous, proteolytically derived peptides as well as peptides non-covalently bound to abundant proteins. We observed differences in peptide profiles associated with Alzheimer鈥檚 disease in the endogenous peptide fraction and in the protein-bound peptide fraction. The discriminating peptides in the unbound peptide fraction were identified as VGF nerve growth factor inducible precursor, and complement C4 precursor, whereas the discriminating peptides in the protein-bound fraction were identified as VGF nerve growth factor inducible precursor, and alpha-2-HS-glycoprotein.