RT Journal Article T1 Prodromic Inflammatory–Oxidative Stress in Peritoneal Leukocytes of Triple-Transgenic Mice for Alzheimer’s Disease A1 Ceprián, Noemí A1 Martínez De Toda Cabeza, Irene A1 Maté, Ianire A1 Garrido, Antonio A1 Giménez Llort, Lydia A1 Fuente Del Rey, María Mónica De La AB Inflammatory–oxidative stress is known to be pivotal in the pathobiology of Alzheimer’s disease (AD), but the involvement of this stress at the peripheral level in the disease’s onset has been scarcely studied. This study investigated the pro-inflammatory profile and oxidative stress parameters in peritoneal leukocytes from female triple-transgenic mice for AD (3xTgAD) and non-transgenic mice (NTg). Peritoneal leukocytes were obtained at 2, 4, 6, 12, and 15 months of age. The concentrations of TNFα, INFγ, IL-1β, IL-2, IL-6, IL-17, and IL-10 released in cultures without stimuli and mitogen concanavalin A and lipopolysaccharide presence were measured. The concentrations of reduced glutathione (GSH), oxidized glutathione (GSSG), lipid peroxidation, and Hsp70 were also analyzed in the peritoneal cells. Our results showed that although there was a lower release of pro-inflammatory cytokines by 3xTgAD mice, this response was uncontrolled and overstimulated, especially at a prodromal stage at 2 months of age. In addition, there were lower concentrations of GSH in leukocytes from 3xTgAD and higher amounts of lipid peroxides at 2 and 4 months, as well as, at 6 months, a lower concentration of Hsp70. In conclusion, 3xTgAD mice show a worse pro-inflammatory response and higher oxidative stress than NTg mice during the prodromal stages, potentially supporting the idea that Alzheimer’s disease could be a consequence of peripheral alteration in the leukocyte inflammation–oxidation state. PB MDPI SN 1661-6596 YR 2024 FD 2024-06-26 LK https://hdl.handle.net/20.500.14352/118618 UL https://hdl.handle.net/20.500.14352/118618 LA eng NO Ceprián, N., Martínez de Toda, I., Maté, I., Garrido, A., Gimenez-Llort, L., & De la Fuente, M. (2024). Prodromic Inflammatory–Oxidative Stress in Peritoneal Leukocytes of Triple-Transgenic Mice for Alzheimer’s Disease. International Journal of Molecular Sciences, 25(13). https://doi.org/10.3390/IJMS25136976 NO This research was supported by grants from MINECO (BFU 2011-30336), the research group UCM (910379 ENEROINN), and FIS (PI15/01787) from the ISCIII-FEDER of the European Union. NO Ministerio de Economía y Competitividad (España) NO Universidad Complutense de Madrid NO Insitituto de Salud Carlos III NO European Commission DS Docta Complutense RD 17 abr 2025