Melanoma cell inoculation improves cognitive impairment in the 5xFAD mouse model of Alzheimer’s diseasedoi:10.34691/UCHILE/UYC3URRepositorio de datos de investigación de la Universidad de Chile2025-12-042Barbara Bruna Jara; Jamileth More; Pedro Lobos Zambrano; Daniela Paz Ponce de la Vega; Claudia Duran-Aniotz; Jose Luis Valdés; Maria Alejandra Gleisner; Fabian Tempio; Felipe Salech; Matías Pizarro; Carol D SanMartín; Martín Cárcamo; Andrew Quest; Mercedes Lopez; Flavio Salazar O; Maria Isabel Behrens, 2025, "Melanoma cell inoculation improves cognitive impairment in the 5xFAD mouse model of Alzheimer’s disease", https://doi.org/10.34691/UCHILE/UYC3UR, Repositorio de datos de investigación de la Universidad de Chile, V2, UNF:6:nVCODfzbWscGFgmS53OoYA== [fileUNF]Melanoma cell inoculation improves cognitive impairment in the 5xFAD mouse model of Alzheimer’s diseasedoi:10.34691/UCHILE/UYC3URBarbara Bruna JaraJamileth MorePedro Lobos ZambranoDaniela Paz Ponce de la VegaClaudia Duran-AniotzJose Luis ValdésMaria Alejandra GleisnerFabian TempioFelipe SalechMatías PizarroCarol D SanMartínMartín CárcamoAndrew QuestMercedes LopezFlavio Salazar OMaria Isabel BehrensRepositorio de datos de investigación de la Universidad de ChileMaría Isabel BehrensBruna Jara, Barbara2025-12-02Medicine, Health and Life SciencesAlzheimerCancerThe inverse association between Alzheimer’s disease (AD) and cancer reported in epidemiological studies remains poorly understood. We injected melanoma B16F0 cells or saline into 5xFAD transgenic AD mice and wildtype (WT) controls and monitored tumor growth and cognitive performance (Y maze, Oasis maze) over 28 days. Melanoma- inoculated 5xFAD mice (5xFAD/B16F0) demonstrated improved cognition compared to 5xFAD/saline, regardless of tumor development, suggesting a systemic immune effect rather than one driven by tumor growth. 5xFAD/B16F0 mice also showed reduced tumor incidence than WT mice, as well as an increased number of splenic myeloid cells. Although amyloid-β levels and the number of astrocytes and microglia were unchanged, microglial soma area in the hippocampus was reduced in 5xFAD/B16F0, suggesting a shift toward a less reactive microglial phenotype. These results suggest that peripheral immune activation may modulate microglia in the hippocampus, offering preliminary insights into the biological basis of the AD and cancer inverse relationship.BB performed the experiments and analyzed, and interpreted the data regarding the experimental studies of cognitive behavior and neuropathological experiments, and was a major contributor in the writing of the manuscript. JM performed the experiments and analyzed and interpreted the data regarding the experimental studies of cognitive behavior and neuropathological experiments, and was a major contributor in the writing of the manuscript. DPP managed the experimental design and analyzed and interpreted the results. CDA contributed to the determination of amyloid staining and analyzed and interpreted the data. PL contributed to the analysis and quantification of amyloid plaque staining. AG performed the immunological analysis in the brains and spleens of transgenic and WT mice. FT performed immunological analysis on the brains and spleens of transgenic and WT mice. FS contributed to the conceptual design of the study and the analysis of the results. MP contributed to the determination of amyloid staining. CSM contributed to the conceptual design of the research and analysis of the results. MC contributed to the conceptual design of the research and analysis of the results. AFGQ contributed to the conceptual design of the research and analysis of the results, ML contributed to the analytic discussion of the immunological results. FS-O contributed to the analytic discussion of the immunological results and text revision. MIB contributed to the experimental design, analysis, and interpretation of the results, and was a major contributor to the writing of the manuscript. All authors read and approved the final manuscript. 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