Pro-inflammatory/Anti-Inflammatory Interleukin Imbalance in Iraqi Alzheimer's Patients: Implications for Post-Conflict Environmental Exposures

Abstract

The role of inflammatory processes has been increasingly recognized in the pathology of Alzheimer's disease (AD), especially in populations with particular environmental exposures. This study examined the profiles of pro-inflammatory (IL-1β, IL-6) and anti-inflammatory (IL-4, IL-10) interleukins in a cohort of 112 Iraqi AD patients and a control group of 240 age-matched subjects. Peripheral blood samples were obtained and analyzed using quantitative real-time PCR and ELISA methods, with correlations made to cognitive performance and degree of amyloid burden. AD patients showed significant upregulation of IL-1β (2.8-fold, p < 0.001) and IL-6 (3.2-fold, p < 0.001) as well as downregulation of IL-10 (0.6-fold, p < 0.01). Interleukin 4 expression was unchanged. Striking correlations were found between pro-inflammatory cytokine expression and cognitive decline measured by the MMSE scores. Increased expression of IL-1β was associated with higher PET imaging-derived amyloid-β deposition. Carriers of the APOE ε4 allele showed a greater degree of inflammatory marker dysregulation compared to non-carriers. A combined model with multiple interleukins achieved superb distinguishing capacity (AUC = 0.94) between AD patients and healthy controls. This study suggests that dysregulation of inflammation likely plays a considerable role in the pathogenesis of AD in the Iraqi population, possibly modified by specific environmental exposures due to decades of conflict. The connection made between peripheral inflammatory markers and central AD pathology underscores the potential value of interleukin expression profiles as accessible biomarkers for prognosis and monitoring. Thus, the connection made between peripheral inflammatory markers and central AD pathology underscores the potential value of interleukin expression profiles as easily obtainable biomarkers for diagnosis and monitoring, which may inform future development of targeted treatment strategies aimed at modulating inflammation in specific populations.