BACKGROUND: Tauopathies represent heterogeneous groups of neurodegenerative diseases that are characterised by abnormal deposition of the microtubule-associated protein tau. Alzheimer's disease is the most prevalent tauopathy, affecting more than 35 million people worldwide. In this study we investigated changes in metabolic pathways associated with tau-induced neurodegeneration. METHODS: Cerebrospinal fluid (CSF), plasma and brain tissue were collected from a transgenic rat model for tauopathies and from age-matched control animals. The samples were analysed by targeted and untargeted metabolomic methods using high-performance liquid chromatography coupled to mass spectrometry. Unsupervised and supervised statistical analysis revealed biochemical changes associated with the tauopathy process. RESULTS: Energy deprivation and potentially neural apoptosis were reflected in increased purine nucleotide catabolism and decreased levels of citric acid cycle intermediates and glucose. However, in CSF, increased levels of citrate and aconitate that can be attributed to glial activation were observed. Other significant changes were found in arginine and phosphatidylcholine metabolism. CONCLUSIONS: Despite an enormous effort invested in development of biomarkers for tauopathies during the last 20 years, there is no clinically used biomarker or assay on the market. One of the most promising strategies is to create a panel of markers (e.g., small molecules, proteins) that will be continuously monitored and correlated with patients' clinical outcome. In this study, we identified several metabolic changes that are affected during the tauopathy process and may be considered as potential markers of tauopathies in humans.

Institute of Molecular and Translational Medicine Faculty of Medicine and Dentistry Palacký University Olomouc Hněvotínská 5 779 00 Olomouc Czech Republic Department of Clinical Biochemistry University Hospital Olomouc 1 P Pavlova 6 775 20 Olomouc Czech Republic

Institute of Molecular and Translational Medicine Faculty of Medicine and Dentistry Palacký University Olomouc Hněvotínská 5 779 00 Olomouc Czech Republic Department of Clinical Biochemistry University Hospital Olomouc 1 P Pavlova 6 775 20 Olomouc Czech Republic Laboratory for Inherited Metabolic Disorders Faculty of Medicine and Dentistry Palacký University Olomouc 1 P Pavlova 6 775 20 Olomouc Czech Republic

Institute of Neuroimmunology Slovak Academy of Sciences Dúbravská cesta 9 84510 Bratislava Slovak Republic AXON Neuroscience R and D Dvořákovo nábrežie 10 811 02 Bratislava Slovak Republic

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