Peripheral infections followed by systemic inflammation may contribute to the onset of Alzheimer`s disease (AD) and accelerate the disease progression later in life. Yet, the impact of systemic inflammation on the plasma and brain tissue metabolome and lipidome in AD has not been investigated. In this study, targeted metabolomic and untargeted lipidomic profiling experiments were performed on the plasma, cortices, and hippocampi of wild-type (WT) mice and transgenic APdE9 mice after chronic lipopolysaccharide (LPS) treatment, as well as saline-treated APdE9 mice. The lipidome and the metabolome of these mice were compared to saline-treated WT animals. In the brain tissue of all three models, the lipidome was more influenced than the metabolome. The LPS-treated APdE9 mice had the highest number of changes in brain metabolic pathways with significant alterations in levels of lysine, myo-inositol, spermine, phosphocreatine, acylcarnitines and diacylglycerols, which were not observed in the saline-treated APdE9 mice. In the WT mice, the effect of the LPS administration on metabolome and lipidome was negligible. The study provided exciting information about the biochemical perturbations due to LPS-induced inflammation in the transgenic AD model, which can significantly enhance our understanding of the role of systemic inflammation in AD pathogenesis.

A 1 Virtanen Institute for Molecular Sciences University of Eastern Finland P O Box 1627 70211 Kuopio Finland

Department of Clinical Biochemistry University Hospital Olomouc 1 P Pavlova 6 77900 Olomouc Czech Republic

Department of Immunobiology University of Arizona 1656 E Mabel Street Tucson AZ 85724 5221 USA

Institute of Molecular and Translational Medicine Palacký University Olomouc Hněvotínská 5 77900 Olomouc Czech Republic

Institute of Pharmacy and Molecular Biotechnology Ruprecht Karls University Im Neuenheimer Feld 329 69120 Heidelberg Germany

Neuroscience Center Helsinki Institute for Life Science University of Helsinki Haartmaninkatu 8 00290 Helsinki Finland

School of Pharmacy University of Eastern Finland P O Box 1627 70211 Kuopio Finland

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