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

• Published in: Methods (San Diego, Calif.) Calif.), 2012-04, Vol.56 (4), p.500-507
• Main Authors: Wijte, Dorien, McDonnell, Liam A., Balog, Crina I.A., Bossers, Koen, Deelder, André M., Swaab, Dick F., Verhaagen, Joost, Mayboroda, Oleg A.
• Format: Article
• Language: English
• Subjects: Aged; Aged, 80 and over; alpha-2-HS-Glycoprotein - cerebrospinal fluid; Alzheimer Disease - cerebrospinal fluid; Alzheimer's disease; Amino Acid Sequence; Area Under Curve; Biomarkers - cerebrospinal fluid; Cerebrospinal fluid; Complement C4 - cerebrospinal fluid; Data Interpretation, Statistical; Endogenous peptides; Female; Humans; Male; Molecular Sequence Data; Molecular Weight; Nerve Growth Factors - cerebrospinal fluid; Peptide Fragments - cerebrospinal fluid; Peptide Fragments - chemistry; Peptide Fragments - isolation & purification; Peptidomics; Principal Component Analysis; Proteome - chemistry; Proteome - isolation & purification; Proteome - metabolism; Proteomics; Reproducibility of Results; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Tandem Mass Spectrometry
• ISSN: 1046-2023; 1095-9130
• DOI: 10.1016/j.ymeth.2012.03.018

Sensitive and specific diagnosis and monitoring of disease progression are of prime importance to develop new therapies for Alzheimer’s disease patients. Although the diagnostic accuracy, verified by pathological examination is high, it is currently not possible to diagnose Alzheimer’s 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’s 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’s 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.