Proteomic Analysis of Cerebrospinal Fluid in Alzheimer's Disease: Wanted Dead or Alive

Article type: Research Article

Authors: Oláh, Zita^{a; *} | Kálmán, János^a | Tóth, Melinda E.^b | Zvara, Ágnes^c | Sántha, Miklós^b | Ivitz, Eszter^a | Janka, Zoltán^a | Pákáski, Magdolna^a

Affiliations: [a] Department of Psychiatry, Faculty of Medicine, University of Szeged, Szeged, Hungary | [b] Laboratory of Animal Genetics and Molecular Neurobiology, Institute of Biochemistry, Biological Research Centre, Szeged, Hungary | [c] Laboratory of Functional Genomics, Biological Research Centre, Szeged, Hungary

Correspondence: [*] Correspondence to: Zita Oláh, Department of Psychiatry, Faculty of Medicine, University of Szeged, 6 Semmelweis street, Szeged H-6724, Hungary. Tel.: +36 62 54 68 51; E-mail: [email protected].

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.

Keywords: Alzheimer's disease, antibody microarray, ApoD, apoptosis, Cdk5, cerebrospinal fluid, granzyme B, MGMT, PAR-4, parkin, POLG

DOI: 10.3233/JAD-140141

Journal: Journal of Alzheimer's Disease, vol. 44, no. 4, pp. 1303-1312, 2015