Title: Identification of Novel Biomarker Candidates by Differential Peptidomics Analysis of Cerebrospinal Fluid in Alzheimers Disease
Volume: 8
Issue: 8
Author(s): Hartmut Selle, Jens Lamerz, Katharina Buerger, Andreas Dessauer, Klaus Hager, Harald Hampel, Johann Karl, Markus Kellmann, Lars Lannfelt, Jukka Louhija, Matthias Riepe, Wolfgang Rollinger, Hayrettin Tumani, Michael Schrader and Hans-Dieter Zucht
Affiliation:
Keywords:
Alzheimer's disease, biological marker, cerebrospinal fluid proteins, differential peptide display, neuropeptides, peptides, peptidomics, proteomics
Abstract: The objective of this work was the application of peptidomics®1 technologies for the detection and identification of reliable and robust biomarkers for Alzheimers 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.
