Association of latent Toxoplasma gondii infection with neuroinflammatory biomarkers and cognitive impairment
Abstract
Latent Toxoplasma gondii infection has been implicated in chronic neuroinflammation and altered neurotrophic signaling, potentially contributing to cognitive dysfunction. This study aimed to investigate the association of latent T. gondii infection with neuroinflammatory biomarkers and cognitive impairment compared with healthy controls. A cross-sectional case–control study was conducted between February 2025 and April 2026, including 100 individuals with latent T. gondii infection and 50 age- and sex-matched healthy controls. Latent infection was confirmed by positive anti- Toxoplasma IgG and negative IgM antibodies using ELISA. Serum levels of interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), S100B protein, high-sensitivity C-reactive protein (hs-CRP), and brain-derived neurotrophic factor (BDNF) were measured using ELISA and immunoturbidimetric assays. Cognitive performance was assessed using the Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), verbal memory, attention, and executive function tests. Participants with latent T. gondii infection showed significantly higher concentrations of IL-6, TNF-α, IL-1β, S100B, and hs-CRP than controls. In contrast, BDNF levels were significantly reduced in the infected group. Cognitive assessments demonstrated significantly lower MMSE, MoCA, memory, attention, and executive function scores among infected individuals, accompanied by a higher prevalence of cognitive impairment. MoCA scores correlated negatively with inflammatory biomarkers and positively with BDNF concentrations. Latent T. gondii infection is associated with increased neuroinflammatory activity, reduced neurotrophic support, and impaired cognitive performance, suggesting that persistent asymptomatic infection may contribute to mild cogn i tive dysfunction through chronic low-grade neuroinflammation.References
Babekir, A., Mostafa, S., & Obeng-Gyasi, E. (2022). The association of Toxoplasma gondii IgG antibody and chronic kidney disease biomarkers. Microorganisms, 10(1), 115.
Bay-Richter, C., Petersen, E., Liebenberg, N., Elfving, B., & Wegener, G. (2019). Latent toxoplasmosis aggravates anxiety- and depressive-like behaviour and suggest a role of gene-environment interactions in the behavioural response to the parasite. Behavioural Brain Research, 364, 133–139.
Castaño Barrios, L., Da Silva Pinheiro, A. P., Gibaldi, D., Silva, A. A., Machado Rodrigues E Silva, P., Roffê, E., da Costa Santiago, H., Tostes Gazzinelli, R., Mineo, J. R., Silva, N. M., & Lannes-Vieira, J. (2021). Behavioral alterations in long-term Toxoplasma gondii infection of C57BL/6 mice are associated with neuroinflammation and disruption of the blood brain barrier. PLoS One, 16(10), e0258199.
Chakroborty, N. K., Baksi, S., & Bhattacharya, A. (2023). Cognitive impairment in parasitic protozoan infection. In: Mukherjee, B., Bhattacharya, A., Mukhopadhyay, R., & Aguiar, B. G. A. (Eds.). Pathobiology of parasitic Protozoa: Dynamics and dimensions. Springer Nature, Singapore. Pp. 61–94.
Colucci-D’Amato, L., Speranza, L., & Volpicelli, F. (2020). Neurotrophic factor BDNF, physiological functions and therapeutic potential in depression, neurodegeneration and brain cancer. International Journal of Molecular Sciences, 21(20), 7777.
Dadkhah, M., Baziar, M., & Rezaei, N. (2024). The regulatory role of BDNF in neuroimmune axis function and neuroinflammation induced by chronic stress: A new therapeutic strategies for neurodegenerative disorders. Cytokine, 174, 156477.
de Haan, L., Sutterland, A. L., Schotborgh, J. V., Schirmbeck, F., & de Haan, L. (2021). Association of Toxoplasma gondii seropositivity with cognitive function in healthy people. JAMA Psychiatry, 78(10), 1103–1112.
Egorov, A. I., Converse, R. R., Griffin, S. M., Styles, J. N., Sams, E., Hudgens, E., & Wade, T. J. (2021). Latent Toxoplasma gondii infections are associated with elevated biomarkers of inflammation and vascular injury. BMC Infectious Diseases, 21, 188.
Ene, L., Marcotte, T. D., Umlauf, A., Grancea, C., Temereanca, A., Bharti, A., Achim, C. L., Letendre, S., & Ruta, S. M. (2016). Latent toxoplasmosis is associated with neurocognitive impairment in young adults with and without chronic HIV infection. Journal of Neuroimmunology, 299, 1–7.
Flegr, J. (2025). Thirty years of studying latent toxoplasmosis: Behavioural, physiological, and health insights. Folia Parasitologica, 72, 5.
Gayger-Dias, V., Vizuete, A. F., Rodrigues, L., Wartchow, K. M., Bobermin, L., Leite, M. C., Quincozes-Santos, A., Kleindienst, A., & Gonçalves, C.-A. (2023). How S100B crosses brain barriers and why it is considered a peripheral marker of brain injury. Experimental Biology and Medicine, 248, 2109–2119.
Gonçalves, L. N. B., Menezes, I. R. R., Palmer, J. L., & Brys, I. (2024). Chronic Toxoplasma gondii infection is associated with decreased working memory performance in women. Estudos de Psicologia, 41, e210112.
Hwang, Y. S., Shin, J.-H., Yang, J.-P., Jung, B.-K., Lee, S. H., & Shin, E.-H. (2018). Characteristics of infection immunity regulated by Toxoplasma gondii to maintain chronic infection in the brain. Frontiers in Immunology, 9, 158.
Kerkis, I., Silva, Á. P. D., & Araldi, R. P. (2024). The impact of interleukin-6 (IL-6) and mesenchymal stem cell-derived IL-6 on neurological conditions. Frontiers in Immunology, 15, 1400533.
Khan, A. W., Farooq, M., Hwang, M.-J., Haseeb, M., & Choi, S. (2023). Autoimmune neuroinflammatory diseases: Role of interleukins. International Journal of Molecular Sciences, 24(9), 7960.
Langeh, U. (2021). Targeting S100B protein as a surrogate biomarker and its role in various neurological disorders. Current Neuropharmacology, 19(2), 265–277.
Latifi, A., & Flegr, J. (2025). Beyond latency: Chronic Toxoplasma infection and its unveiled behavioral and clinical manifestations – a 30-year research perspective. Biomedicines, 13(7), 1731.
Lu, Y. (2025). Response letter to “Cumulative infection burden, cognitive impairment and dementia”. Brain, Behavior, and Immunity, 123, 606.
Matta, S. K., Rinkenberger, N., Dunay, I. R., & Sibley, L. D. (2021). Toxoplasma gondii infection and its implications within the central nervous system. Nature Reviews Microbiology, 19(7), 467–480.
Mendez, O. A., & Koshy, A. A. (2017). Toxoplasma gondii: Entry, association, and physiological influence on the central nervous system. PLoS Pathogens, 13(7), e1006351.
Nayeri, T., Sarvi, S., & Daryani, A. (2024). Effective factors in the pathogenesis of Toxoplasma gondii. Heliyon, 10(10), e31558.
Ramírez-Flores, C. J., & Mondragón-Flores, R. (2025). Comprehensive analysis of Toxoplasma gondii migration routes and tissue dissemination in the host. PLoS Neglected Tropical Diseases, 19(7), e0013369.
Robert-Gangneux, F., & Guegan, H. (2021). Anti-Toxoplasma IgG assays: What performances for what purpose? A systematic review. Parasite, 28, 39.
Sanchez, S. G., & Besteiro, S. (2021). The pathogenicity and virulence of Toxoplasma gondii. Virulence, 12(1), 3095–3114.
Sarkar, S., Porel, P., Kosey, S., & Aran, K. R. (2025). Diverse role of S100 calcium-binding protein B in Alzheimer’s disease: Pathological mechanisms and therapeutic implications. Inflammopharmacology, 33(4), 1803–1816.
Shi, R., Yu, S., Larbi, A., Pin Ng, T., & Lu, Y. (2024). Specific and cumulative infection burden and mild cognitive impairment and dementia: A population-based study. Brain, Behavior, and Immunity, 121, 155–164.
Shi, W.-Q., Bai, S.-Y., Pan, M., Jin, Q.-W., Liu, Z., Bo, X., & Huang, S.-Y. (2025). Chronic toxoplasmosis induces depression-like behaviors and neuroinflammatory responses in mice. Acta Tropica, 264, 107568.
Silakarma, D., & Sudewi, A. A. R. (2019). The role of brain-derived neurotrophic factor (BDNF) in cognitive functions. Bali Medical Journal, 8(2), 518–525.
Silva, A. R., Regueira, P., Cardoso, A. L., Baldeiras, I., Santana, I., & Cerejeira, J. (2021). Cognitive trajectories following acute infection in older patients with and without cognitive impairment: An 1-year follow-up study. Frontiers in Psychiatry, 12, 754489.
Vergne-Salle, P., & Bertin, P. (2021). Chronic pain and neuroinflammation. Joint Bone Spine, 88(6), 105222.
Xiao, J. (2022). Behavioral changes induced by latent toxoplasmosis could arise from CNS inflammation and neuropathogenesis. In: Savitz, J., & Yolken, R. H. (Eds.). Microorganisms and mental health. Springer, Cham. Pp. 303–313.
Zhao, X.-Y., & Ewald, S. E. (2020). The molecular biology and immune control of chronic Toxoplasma gondii infection. Journal of Clinical Investigation, 130(7), 3370–3380.
Zvonarev, V., Mamtani, S., Yadav, S., Sharazi, K., Syed, H., Giri, A., Rodas, A., Tregubenko, P., & Kotler, D. (2020). Neurocognitive performance of African Americans and Hispanic adults in relation to diet and physical activity: A literature review. Journal of Neurology Research, 10(3), 56–68.
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