Assessment of Neuroinflammatory Markers (IL-6, TNF-α) and Cognitive Decline in Early Alzheimer’s Disease Patients

Authors

  • FEHMIDA BIBI Special Infectious Agents Unit–BSL3, King Fahd Medical Research Centre, King Abdulaziz University, Jeddah 21589, Saudi
  • IKRAM ULLAH Center for Interdisciplinary Research in Basic Sciences International Islamic University Islamabad
  • MUHAMMAD IMRAN NASEER Institute of Genomic Medicine Sciences (IGMS), King Abdulaziz University, Jeddah 21589, Saudi Arabia

DOI:

https://doi.org/10.53350/pjmhs02026204.5

Keywords:

Alzheimer disease, IL-6, TNF-α, neuroinflammation, cognitive decline, biomarkers.

Abstract

Background: Alzheimer disease is a progressive neurodegenerative disorder characterized by premature deterioration of the brain and progressive memory impairment. Emerging evidence suggests that neuroinflammation plays a central role in the pathogenesis of the disease, with pro-inflammatory cytokines such as interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) contributing to neuronal dysfunction and cognitive decline.

Objective: To measure serum IL-6 and TNF-α levels in patients with early-stage Alzheimer disease and to determine their association with cognitive deterioration.

Methods: This cross-sectional comparative study was conducted at a tertiary care hospital from March 2023 to February 2025. A total of 70 participants were enrolled, including 40 patients with early Alzheimer disease and 30 cognitively healthy controls. Cognitive performance was assessed using the Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA). Serum IL-6 and TNF-α levels were measured using enzyme-linked immunosorbent assay (ELISA). Statistical analysis was performed using SPSS version 26, and correlations were assessed using Pearson’s correlation coefficient.

Results: Patients with early Alzheimer disease had significantly lower cognitive scores than controls (MMSE: 21.48 ± 2.86 vs 28.27 ± 1.41; MoCA: 18.94 ± 3.17 vs 26.31 ± 1.84; p = 0.001). Serum IL-6 and TNF-α levels were significantly elevated in the Alzheimer group (IL-6: 8.61 ± 2.49 pg/mL vs 4.29 ± 1.47 pg/mL; TNF-α: 14.87 ± 4.12 pg/mL vs 8.64 ± 2.31 pg/mL; p < 0.001). Both cytokines demonstrated significant negative correlations with MMSE and MoCA scores, indicating that higher inflammatory marker levels were associated with poorer cognitive performance.

Conclusion: Elevated serum IL-6 and TNF-α levels in early Alzheimer disease are significantly associated with cognitive decline. These findings support the role of neuroinflammation in Alzheimer disease progression and suggest that these inflammatory markers may serve as accessible biomarkers for early disease monitoring and prognostic evaluation.

References

Wang H, Shen Y, Chuang H, Chiu C, Ye Y, Zhao L. Neuroinflammation in Alzheimer’s disease: microglia, molecular participants and therapeutic choices. Curr Alzheimer Res. 2019;16(7):659-674. doi:10.2174/1567205016666190503151648

Su C, Zhao K, Xia H, Xu Y. Peripheral inflammatory biomarkers in Alzheimer’s disease and mild cognitive impairment: a systematic review and meta-analysis. Psychogeriatrics. 2019;19(4):300-309. doi:10.1111/psyg.12403

Taipa R, das Neves SP, Sousa AL, Fernandes J, Pinto C, Correia AP, et al. Proinflammatory and anti-inflammatory cytokines in the CSF of patients with Alzheimer’s disease and their correlation with cognitive decline. Neurobiol Aging. 2019;76:125-132. doi:10.1016/j.neurobiolaging.2018.12.019

Ji Y, Wang X, Kalicki C, Menta BW, Baumgardner M, Koppel SJ, et al. Effects of microglial cytokines on Alzheimer’s disease-related phenomena. J Alzheimers Dis. 2019;67(3):1021-1034. doi:10.3233/JAD-180820

Sharman MJ, Verdile G, Kirubakaran S, Parenti C, Singh A, Watt G, et al. Targeting inflammatory pathways in Alzheimer’s disease: a focus on natural products and phytomedicines. CNS Drugs. 2019;33(5):457-480. doi:10.1007/s40263-019-00619-1

Janelidze S, Palmqvist S, Leuzy A, Stomrud E, Verberk IMW, Zetterberg H, et al. Detecting amyloid positivity in early Alzheimer’s disease using combinations of plasma Aβ42/Aβ40 and p-tau. Nat Commun. 2022;13:7152. doi:10.1038/s41467-022-34669-6

Chai YL, Lee JH, Chong JR, Ballard C, Francis PT, Kennedy BK, et al. Inflammatory panel cytokines are elevated in the neocortex of late-stage Alzheimer’s disease but not Lewy body dementias. J Neuroinflammation. 2023;20(1):111. doi:10.1186/s12974-023-02789-8

Chen X, Zhang M, Ahmed M, Surapaneni KM, Veeraraghavan VP, Arulselvan P. The role of IL-6 in neurodegenerative disorders. Mol Neurobiol. 2024;61(6):3211-3230. doi:10.1007/s12035-024-03957-5

Serna MF, Castañeda-Cardona C, Morelli L, Rodríguez de Fonseca F, Politis DG, Brusco LI, et al. Inflammatory markers and their relationship with cognitive function in Alzheimer’s disease and mild cognitive impairment: systematic review and meta-analysis. Neuromolecular Med. 2025. doi:10.1007/s12017-025-08840-4

Campanelli L, Galeano P, Prestia FA, Cuesta C, Dalmasso MC, Flores-López M, et al. Blood levels of cytokines highlight the role of inflammation in Alzheimer’s disease. Heliyon. 2025;11(2):e41725. doi:10.1016/j.heliyon.2025.e41725

Heneka MT, Gauthier S, Chandekar SA, Hahn-Pedersen JH, Bentsen MA, Zetterberg H. Neuroinflammatory fluid biomarkers in patients with Alzheimer’s disease: a systematic literature review. Mol Psychiatry. 2025. doi:10.1038/s41380-025-02944-7

Aljuhani M. Cerebrospinal fluid levels of tumour necrosis factor-α and its receptors are not associated with disease progression in Alzheimer’s disease. Front Aging Neurosci. 2025;17:1547185. doi:10.3389/fnagi.2025.1547185

Ghanbarian E, Khorsand B, Petersen KK, Nallapu BT, Sajjadi SA, Lipton RB, et al. Cerebrospinal fluid inflammatory cytokines as prognostic indicators for cognitive decline across Alzheimer’s disease spectrum. J Alzheimers Dis. 2025;105(4):1298-1308. doi:10.1177/13872877251335915

Yasuno F, Watanabe A, Kimura Y, Yamauchi Y, Ogata A, Ikenuma H, et al. Plasma IL-6 levels as a biomarker for behavioral changes in Alzheimer’s disease. Neuroimmunomodulation. 2025. doi:10.1159/000547726

Zhang P, Wu N, Xue Q, Li J, Ouyang Q, Yu X, et al. Plasma leptin, resistin, tumor necrosis factor-alpha, and interleukin-6 with risk of dementia: a prospective population study. J Alzheimers Dis. 2025;106(4):1475-1485. doi:10.1177/13872877251352480

Qin Q, Xia X, Qu J, Guan Z, Yin Y, Chang J, et al. Blood biomarkers of amyloid and tau pathologies, brain degeneration, inflammation, and oxidative stress in early- and late-onset Alzheimer’s disease. J Alzheimers Dis. 2025;108(1 Suppl):S28-S41. doi:10.1177/13872877251340955

Kowalska A, Wysocka A, Głowacka E, Stępień A, Mroczek T, Dulski J, et al. Neuroinflammation as a link in Parkinson’s and Alzheimer’s diseases: a systematic review and meta-analysis. Int J Mol Sci. 2024;25(24):13244. doi:10.3390/ijms252413244

Cummings J, Apostolova LG, Rabinovici GD, Atri A, Aisen P, Greenberg S, et al. Lecanemab: appropriate use recommendations. J Prev Alzheimers Dis. 2023;10(3):362-377. doi:10.14283/jpad.2023.30

Moscoso A, Grothe MJ, Ashton NJ, Karikari TK, Lantero Rodríguez J, Snellman A, et al. Longitudinal associations of blood phosphorylated tau181 and neurofilament light chain with neurodegeneration in Alzheimer’s disease. Brain. 2021;144(11):3486-3497. doi:10.1093/brain/awab315

Palmqvist S, Tideman P, Cullen N, Zetterberg H, Blennow K, Dage JL, et al. Prediction of future Alzheimer’s disease dementia using plasma phospho-tau combined with other accessible measures. Nat Med. 2021;27(6):1034-1042. doi:10.1038/s41591-021-01348-z

Downloads

Crossmark - Check for Updates

How to Cite

BIBI, F. ., ULLAH, I. ., & NASEER, M. I. . (2026). Assessment of Neuroinflammatory Markers (IL-6, TNF-α) and Cognitive Decline in Early Alzheimer’s Disease Patients. Pakistan Journal of Medical & Health Sciences, 20(4), 26–32. https://doi.org/10.53350/pjmhs02026204.5