Affiliations: [a]
Institute of Neuroimmunology, Slovak Academy of Sciences, Bratislava, Slovak Republic | [b] AXON Neuroscience R&D, Bratislava, Slovak Republic | [c] Department of Pharmacology and Toxicology, The University of Veterinary Medicine and Pharmacy, Kosice, Slovak Republic | [d]
Institute of Chemistry, Slovak Academy of Sciences, Bratislava, Slovak Republic | [e] Institute of Mathematics and Statistics, Faculty of Science, Masaryk University, Brno, Czech Republic
Correspondence:
[*]
Correspondence to: Andrej Kovac, Institute of Neuroimmunology, Slovak Academy of Sciences, Dubravska cesta 9, 84510, Bratislava, Slovak Republic. Tel.: +421 2 5478 8100; Fax: +421 2 5477 4276; E-mail: andrej.kovac@savba.sk.
Abstract: Alzheimer’s disease (AD) and progressive supranuclear palsy are two common neurodegenerative tauopathies, and the most common cause of progressive brain dementia in elderly affecting more than 35 million people. The tauopathies are characterized by abnormal deposition of microtubule associated protein tau into intracellular neurofibrillary tangles composed mainly of the hyperphosphorylated form of the protein. The diagnosis of tauopathies is based on the presence of clinical features and pathological changes. Over the last decade, there has been an intensive search for novel biochemical markers for clinical diagnosis of AD and other tauopathies. In the present study, we used transgenic rat model for tauopathy expressing human truncated tau protein (aa 151–391/4R) to analyze the cerebrospinal fluid (CSF) peptidome using liquid chromatography – matrix assisted laser desorption/ionization mass spectrometry (LC-MALDI TOF/TOF). From 345 peptides, we identified a total of 175 proteins. Among them, 17 proteins were significantly altered in the CSF of transgenic rats. The following proteins were elevated in the CSF of transgenic rats when compared to the control animals: neurofilament light and medium chain, apolipoprotein E, gamma-synuclein, chromogranin A, reticulon-4, secretogranin-2, calsyntein-1 and -3, endothelin-3, neuroendocrine protein B72A, alpha-1-macroglobulin, and augurin. Interestingly most of the identified proteins were previously linked to AD and other tauopathies, indicating the significance of transgenic animals in biomarker validation.
Keywords: Cerebrospinal fluid, LC-MALDI MS, peptidomics, rat model, tauopathy
