title: Proteomic analysis of cerebrospinal fluid in Alzheimer's disease: wanted dead or alive.
abstract: Clinical diagnosis of Alzheimer's disease (AD) relying on symptomatic features has a low specificity, emphasizing the importance of the pragmatic use of neurochemical biomarkers. The most advanced and reliable markers are amyloid-β (Aβ42), total tau (t-tau), and phosphorylated tau (p-tau) in cerebrospinal fluid (CSF) with relatively high levels of sensitivity, specificity, and diagnostic accuracy. Recent advances within the field of proteomics offer the potential to search for novel biomarkers in CSF by using modern methods, such as microarrays. The purpose of this study was to identify pathognostic proteins in CSF obtained from patients whose clinical AD diagnosis was confirmed by the "core" biomarkers. CSF samples were obtained from 25 AD patients and 25 control individuals. The levels of Aβ42, t-tau, and p-tau were measured by ELISA. In the microarray experiments, ultrasensitive slides representing of 653 antigens were used. Apolipoprotein E genotyping was also determined. A decrease of seven CSF proteins in AD were found, four of them (POLG, MGMT, parkin, and ApoD) have a protective function against neuronal death, while the remaining three proteins (PAR-4, granzyme B, Cdk5) trigger multiple pathways facilitating neuronal cell death. Since these proteins from CSF samples could not be identified by western blot, their decreased levels in AD patients were not verified. Our results provide new information of pathognostic importance of POLG and granzyme B in AD. Although the function of MGMT, parkin, ApoD, PAR-4, and Cdk5 was previously known in AD, the findings presented here provide novel evidence of the significance of CSF analysis in the mapping of the AD pathomechanism.
authors.affiliation: Department of Psychiatry, Faculty of Medicine, University of Szeged, Szeged, Hungary.
authors.forename: Zita
authors.initials: Z
authors.lastname: Oláh
authors.affiliation: Department of Psychiatry, Faculty of Medicine, University of Szeged, Szeged, Hungary.
authors.forename: János
authors.initials: J
authors.lastname: Kálmán
authors.affiliation: Laboratory of Animal Genetics and Molecular Neurobiology, Institute of Biochemistry, Biological Research Centre, Szeged, Hungary.
authors.forename: Melinda E
authors.initials: ME
authors.lastname: Tóth
authors.affiliation: Laboratory of Functional Genomics, Biological Research Centre, Szeged, Hungary.
authors.forename: Ágnes
authors.initials: Á
authors.lastname: Zvara
authors.affiliation: Laboratory of Animal Genetics and Molecular Neurobiology, Institute of Biochemistry, Biological Research Centre, Szeged, Hungary.
authors.forename: Miklós
authors.initials: M
authors.lastname: Sántha
authors.affiliation: Department of Psychiatry, Faculty of Medicine, University of Szeged, Szeged, Hungary.
authors.forename: Eszter
authors.initials: E
authors.lastname: Ivitz
authors.affiliation: Department of Psychiatry, Faculty of Medicine, University of Szeged, Szeged, Hungary.
authors.forename: Zoltán
authors.initials: Z
authors.lastname: Janka
authors.affiliation: Department of Psychiatry, Faculty of Medicine, University of Szeged, Szeged, Hungary.
authors.forename: Magdolna
authors.initials: M
authors.lastname: Pákáski
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid* / Q000175:diagnosis / Q000235:genetics; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid*; D053399:Apolipoproteins D / Q000134:cerebrospinal fluid; D001057:Apolipoproteins E / Q000235:genetics; D015415:Biomarkers / Q000134:cerebrospinal fluid*; D015254:DNA Modification Methylases / Q000134:cerebrospinal fluid; D000074002:DNA Polymerase gamma; D045643:DNA Repair Enzymes / Q000134:cerebrospinal fluid; D004259:DNA-Directed DNA Polymerase / Q000134:cerebrospinal fluid; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D010446:Peptide Fragments / Q000134:cerebrospinal fluid*; D040081:Protein Array Analysis; D040901:Proteomics; D012680:Sensitivity and Specificity; D015898:Tomography Scanners, X-Ray Computed; D025521:Tumor Suppressor Proteins / Q000134:cerebrospinal fluid; D044767:Ubiquitin-Protein Ligases / Q000134:cerebrospinal fluid; D016875:tau Proteins / Q000134:cerebrospinal fluid*
chemical_list: C024328:APOD protein, human; D016229:Amyloid beta-Peptides; D053399:Apolipoproteins D; D001057:Apolipoproteins E; D015415:Biomarkers; D010446:Peptide Fragments; D025521:Tumor Suppressor Proteins; C075222:amyloid beta-protein (1-42); D016875:tau Proteins; D015254:DNA Modification Methylases; C515491:MGMT protein, human; D044767:Ubiquitin-Protein Ligases; C111567:parkin protein; D000074002:DNA Polymerase gamma; D004259:DNA-Directed DNA Polymerase; C413027:POLG protein, human; D045643:DNA Repair Enzymes
keywords: Alzheimer's disease; ApoD; Cdk5; MGMT; PAR-4; POLG; antibody microarray; apoptosis; cerebrospinal fluid; granzyme B; parkin