Identification of Novel Biomarker Candidates by Differential Peptidomics Analysis of Cerebrospinal Fluid in Alzheimers Disease

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; Hans-Dieter      Zucht

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.

Keywords: Alzheimer's disease, biological marker, cerebrospinal fluid proteins, differential peptide display, neuropeptides, peptides, peptidomics, proteomics