Identification of novel biomarker candidates by differential peptidomics analysis of cerebrospinal fluid in Alzheimer's disease.
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.
Selle
Hartmut
H
BioVisioN AG, 30625 Hannover, Germany. h.selle@peptidomics.de
Lamerz
Jens
J
Buerger
Katharina
K
Dessauer
Andreas
A
Hager
Klaus
K
Hampel
Harald
H
Karl
Johann
J
Kellmann
Markus
M
Lannfelt
Lars
L
Louhija
Jukka
J
Riepe
Matthias
M
Rollinger
Wolfgang
W
Tumani
Hayrettin
H
Schrader
Michael
M
Zucht
Hans-Dieter
HD
D000465:Algorithms; D000595:Amino Acid Sequence; D002851:Chromatography, High Pressure Liquid; D006801:Humans; D008956:Models, Chemical; D008969:Molecular Sequence Data; D036103:Nanotechnology; D016571:Neural Networks, Computer; D010447:Peptide Hydrolases / Q000737:chemistry; D010455:Peptides / Q000134:cerebrospinal fluid* / Q000737:chemistry; D021241:Spectrometry, Mass, Electrospray Ionization; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
D010455:Peptides; D010447:Peptide Hydrolases